Dual Icons in Health Care: Better Living Through Chemistry and the Holy Grail

Back in 1935, the giant chemical manufacturer DuPont proclaimed a new era of discovery and product development with the slogan, "Better Things for Better Living ...Through Chemistry." Shortly afterward, to avoid copyright infringement, the slogan, "Better Living Through Chemistry" became so widespread that it quickly overwhelmed its predecessor.¹ It even found its way into the renowned psychedelic poster that burst upon the scene at the zenith of the American psychedelic culture emerging from the Haight-Ashbury district of San Francisco in 1967, featuring a group of tripping denizens after they had dropped a sugar cube of acid. More recently, the phrase has been embraced by such rock groups as Queen of the Stone Age, Ademan, and Fear of Music. A second stream of this narrative has to do with the Holy Grail, the famed cauldron endowed with special powers and the quest of which became a key narrative element in the Arthurian cycle relating events in British history in the 5th and 6th centuries.²

These two icons – Better Living Through Chemistry and the Holy Grail – join in holy matrimony when we consider some of the most significant conceptual advances in health care in general and chiropractic in particular. The icons have everything to do with a chemical substance and the molecule that receives it in the human body. Accordingly, this type of thinking has led to the discovery and understanding of important new compounds and mechanisms that need to be regarded as key components in health care – including chiropractic.

1. For openers, consider how homeopathic dilutions well beyond Avogadro's number could be rationalized to exert clinical effects. Researchers have applied such terms as signature or signifiers to attempt to explain how a particular homeopathic remedy could have exerted its effects well past the time it could have remained in solution after massive dilutions.³ The intense head-scratching that this logic has created has gone so far as to have led others to conclude that "normal science has to be abandoned," going so far as to construct a Bayesian analysis to describe how scientists "ought rationally to change their prior beliefs in light of the evidence."⁴
   
   But maybe not. After hearing a seminar by David O'Reilly, a leading homeopathic researcher, in 1996, I had the presence of mind to ask him whether the substance used in the dilutions had to be a polar solvent. His answer was an emphatic yes. O'Reilly's reply opened a whole new line of thinking with the potential to put homeopathic back on the tracks of traditional scientific thinking. This is because water, a polar solvent, has been known for some time to form clathrates, or cages, around a solute that has long since disappeared.⁵ This raises the possibility that this is precisely what has happened in the homeopathic dilutions, such that it is the water clathrate that has exerted its effect so that we now could postulate a more traditional chemical basis as to what has happened in homeopathic treatment.
   


2. To continue, think about morphine and its palliative effects upon pain. Unfortunately, the well-known side effect is that morphine is habit-forming. Enter Candace Pert, who had the foresight to realize that the molecules which bind morphine (opiate receptors) signal that there must be naturally occurring substances that resemble morphine in structure, since receptors wouldn't be manufactured in the body simply to bind a synthetic drug. This led directly to the discovery of the endorphins (enkephalins)⁶ as the naturally occurring analogs to morphine; as such, they are not habit-forming and reveal an important biological mechanism for suppressing pain and creating a sense of well-being.
   
   Applying a line of reasoning that is clearly chemical, Pert followed the principle of "reverse engineering" to craft and search for a molecule to fit the opiate receptor, arriving at the discovery of not only a new regulatory pathway in the body, but also of a compound that could be extracted and used clinically without the detrimental side effects of morphine.
   


3. The entire field of hormone action was revolutionized with the discovery of the estrogen receptor in 1968 by two teams of researchers, led by McGuire⁷ and Gorski.⁸ The concept of receptors not only provided an explanation as to the specificity and dynamics of estrogen action, but shortly afterward also extended to the means by which breast cancers could be differentiated and effectively treated by hormone therapy,^9-10 a staple by which several forms of breast cancer have since been successfully treated.
   


4. The analgesic effect of acupuncture has been successfully replicated in animal models with the injection of an adenosine A1 receptor agonist, while inhibition of enzymes involved in adenosine degradation potentiated the acupuncture-elicited increase in adenosine – as well as its anti-nociceptive effect. In other words, a biochemical intermediate as a neuromodulator and its receptor were able to capture the essence of acupuncture and repeat its beneficial effects in experimental rats.¹¹
   


5. Extending these concepts to neural stimulation and the essence of chiropractic, it can be argued that a variety of receptors initiate afferent stimuli that affect all motor pathways either indirectly or indirectly through their action upon suprasegmental targets. It has been argued that the central integrative state of virtually all neuron pools is affected by the firing of groups of sensory receptors.¹² The gustatory response that comprises a component of applied kinesiology has been recently postulated to be mediated by two parallel pathways, one discriminating basic taste qualities (sweet, bitter, sour, salty, savory) and perceiving flavors; the other conducting information involved in such physiological reflexes as swallowing, salivation, and cephalic phase digestion. A variety of receptors have been shown to mediate these pathways.¹³

Summing up, it would be tragically premature to dismiss the importance of chemical intermediates and their receptors in evaluating the effectiveness of chiropractic. Indeed, our previous discussions of enkephalins may have come full circle to chiropractic by the preliminary observations that these substances are found to increase for a brief period following spinal manipulation.¹⁴ The topic of hormone action connects to chiropractic or massage by the reports that: 1) cortisol levels decrease after spinal manipulation¹⁵ or massage;¹⁶ 2) prostaglandin levels known to cause uterine cramping may decline after side-posture manipulation;¹⁷ 3) aldosterone concentrations appear to fall following spinal manipulation;¹⁸ and 4) the inflammatory neuropeptides tumor necrosis factor alpha, interleukin-1 beta¹⁹ and interleukin-6²⁰ all decrease following spinal manipulation accompanied by cavitation.

Even though subluxation has been traditionally considered to be the Holy Grail in numerous chiropractic circles, we have to consider such broader areas of concern as nutritional deficiencies, stress and immunity, in which chemical intermediates and their receptors play an integral part. Clearly, they can be identified as sequelae to manipulation in several instances, so that while one attempts to pin down the exact nature of the subluxation, it is worth considering the chemical intermediates and their receptors as handmaidens at worst and perhaps portions of the subluxation at best.

Thus, one can actually propose that the time-honored mantra "Better Living Through Chemistry" must extend to future efforts in chiropractic research in order for the profession to remain viable and conversant with medical research as well. Come to think of it, the receptor itself as a vessel for specifically binding to classes of biochemical intermediates could be considered to be an updated, 21^st century physiological Holy Grail.

References

1. Alatzas T. "DuPont Touts 'Miracles'." The News Journal, April 4, 1999; p. 29.
2. Loomis RS. The Grail From Celtic Myth to Christian Symbol. Princeton University Press, Princeton, NJ, 1991.
3. Bastide M, Lagache A. A communication process: a new paradigm applied to high-dilution effects on the living body. Alternative Therapies in Health and Medicine, 1997;3(4):35-39.
4. Vallance AK. Can biological activity be maintained at ultra-high dilution? An overview of homeopathy, evidence, and Bayesian philosophy. Journal of Alternative and Complementary Medicine, 1998;4(1):49-76.
5. Valtheeswaran S, Yin H. Rasajah JC, Hummer G. Water clusters in nonpolar cavities. Proceedings of the National Academy of Sciences, 2004;101(49):17002-17005.
6. Bowen WD, Gentleman S, Herkenham M, Pert CB. Interconverting mu and delta forms of the opiate receptor in rat striatal patches. Proceedings of the National Academy of Sciences, 1981;78(8): 4818-4822.
7. McGuire JL, Lisk RD. Estrogen receptors in the intact rat. Proceedings of the National Academy of Sciences, 1968;61(2):497-503.
8. Gorski J, Toft D, Shyamala G, Smith D, Notides A. Hormone receptors: studies on the interaction of estrogen with the uterus. Recent Progress in Hormone Research, 1968;24:45-80.
9. Jensen EV, Block GE, Smith S, Kyseer K, Desombre ER. Estrogen receptors and breast cancer response to adrenalectomy. National Cancer Institute Monograph, 1971;34:55-70.
10. Hahnel R, Twaddle E, Vivian AB. Estrogen receptors in human breast cancer: 2: in vitro binding of estradiol by benign and malignant tumors. Steroids, 1971;18(6):681-708.
11. Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W, Jensen TK, Pei Y, Wang F, Han X, Chen J-F, Schnermann J, Takano T, Bekar L, Tieu K, Nedergaard M. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nature Neuroscience, 2010;13(7):883-889.
12. Schmitt WH, Yanuck SF. Expanding the neurological examination using functional neurological assessment: part II neurologic basis of applied kinesiology. International Journal of Neuroscience, 1999;97:77-108.
13. Roper SD. Parallel processing in mammalian taste buds? Physiology & Behavior, 2009;97 604-608.
14. Vernon HT, Dhami MSI, Howley TP, Annett R. Spinal manipulation and beta-endorphin: a controlled study  of the effect of a spinal manipulation on plasma beta-endorphin levels in normal males. Journal of Manipulative and Physiological Therapeutics, 1986;9(2):115-123.
15. Ali S, Hayek R, Holland R, McKelvey S-E, Boyce K. Effect of chiropractic treatment on the endocrine and immune system in asthmatic patients. Proceedings of the 2002 International Conference on Spinal Manipulation, Toronto, Ontario, Canada, Oct. 4-5, 2002:57-58.
16. Field T, Henteleff T, Hernandez M, Martinez E, Mavunda K, Kuhn C, Schanberg S. Children with asthma improved pulmonary functions after massage therapy. Journal of Pediatrics, 1998;32(5):854-858.
17. Kokjohn K, Schmid DM, Triano JJ, Brennan PC. The effect of spinal manipulation on pain and prostaglandin levels in women with primary dysmenorrhea. Journal of Manipulative and Physiological Therapeutics, 1992;15(5):279-285.
18. Wagnon RJ, Sandefur RM, Ratliff CR. Serum aldosterone changes after specific chiropractic manipulation. American Journal of Chiropractic Medicine, 1988;1(2):66-70.
19. Teodorscyzk-Injeyan J, Injeyan HS, Ruegg R. Spinal manipulative therapy reduces inflammatory cytokines but not substance P production in normal subjects. Journal of Manipulative and Physiological Therapeutics, 2006;29(1):14-21.
20. Teodorscyzk-Injeyan J, Injeyan HS, Ruegg R. Spinal manipulative therapy (SMT) augments production of anti-inflammatory cytokine IL-10 in normal subjects. Proceedings of the 9th Biennial Congress of the World Federation of Chiropractic, Vilamoura, Portugal, May 17-19, 2007:143-144.