Mechanism: Experimental Approaches to Understanding Acupuncture, Part 2
By Shai White-Gilbertson, PhD, MSCR, Dipl Ac, CTR
Biomedical research takes for granted that the best way to cleanly and rigorously study any phenomenon is to experimentally isolate it, something which has proven to be difficult in clinical acupuncture studies.
For example, the problem of how to create a sham acupuncture treatment has troubled researchers for decades, on both sides of the acupuncture/allopathic divide. The complex experimental system embodied by any patient synthesizes responses to a wide array of experiences; definitively creating a control acupuncture experience for such a complex system has been challenging. However, thanks to the flexibility and sensitivity of available tools, today we can study a simple cellular response to acupuncture. Reducing an experimental framework to simple cells could certainly strike holistic healers as absurdly disconnected from the energetic nuances of human health, and this is a valid concern. I'll describe representative possible experiments here, and the information that could be obtained may appeal to the imaginations of people from diverse training and backgrounds.
One recent hypothesis about cellular response to acupuncture is the micro-damage hypothesis. This suggests that the mechanical stress of needle insertion and manipulation causes a signaling cascade inside the body.1,2 The micro-damage hypothesis indirectly references a fascinating aspect of cellular biology called "lysosomal exocytosis". Lysosomal exocytosis is a cellular behavior I studied for a few years under the direction of Dr. Alessandra d'Azzo and I learned that this phenomenon is linked in some way to much of cellular physiology.3
Lysosomes are constituent parts of our cells, like nuclei and mitochondria. They are multi-functional but most commonly known for being the recycling center of the cell, where old or faulty components are sent to be stripped for parts. Thus, the interior of a lysosome contains a snapshot of how things are going for that cell. Is a certain class of protein being turned over at an increased rate? Has a certain protein failed quality control over and over? Lysosomes are charged with processing such proteins. This normal duty is interesting enough but under micro-damaging circumstances, the lysosomal population can do a really amazing trick. Lysosomes rush to the site of injury, where a tear in the cell membrane has occurred, and they fuse their membranes to the greater cell membrane to create a patch.4 When their normal spherical shape is pulled apart to create a flat patch, the contents of the lysosomes get released into the extracellular space, spilling the most intimate information about that cell's status. This capacity may mediate some of the body's response to acupuncture, and some investigation could be done very directly.
It is fairly trivial to maintain a population of skin cells or connective tissue cells — or a blend — in a dish. Cells grown in the lab are bathed in a type of nutritious fluid called "media." A population of cells that undergo micro-damage will likely, subsequently experience lysosomal exocytosis and information about the cells' interior life will escape into the media. We now live in an age when this media can be collected and analyzed with incredible precision, helping us to understand the type of information released from cells. Additionally, it is possible to grow cells in stressed environments. They can be under-fed by using less nutritious media. They can be kept in a low-oxygen environment. Their media can be spiked with a wide assortment of drugs, both therapeutic and harmful. Any of these cell populations could be micro-damaged, even using a grid of actual acupuncture needles. If differently stressed populations release measurably different signals into the media, it would validate the idea that minimally damaging techniques can foster communication that describes cellular health.
The second step which would interest me would require an additional piece of equipment and one more ingredient, both easy to come by and work with in the lab. The equipment is a fine mesh. It supports an experimental design called a transwell experiment, and meshes of many varieties exist, allowing researchers to choose exact specifications for the mesh permeability. The needed ingredient is a panel of normal healthy blood cells, which can also be maintained in dishes in the lab. To assemble the experiment, simply micro-damage a group of test cells and then overlay the mesh. On top of the mesh, place the blood cells. Blood cells are able to squeeze through small openings when motivated; this is how an immune cell traveling through the blood stream gets past the lining of a blood vessel and finds its target in tissue. If micro-damaged cells are releasing interpretable information, blood cells above the mesh will respond and migrate toward the damage. A different variety of blood cells might even respond, depending on what sort of stress situation the cells are reporting, whether the cells are cold, or hungry, or drugged.
If we can study response from one bodily intelligence, in this instance the blood cell population, to a simple release of status information from cells in a dish, we could establish something basic, something measurable, on which to build further discussion and exploration. It could provide an empirical analysis of the information released by acupuncture and fuel desire to ask more integrated questions. What about anatomical and chemical networks make certain information releasable from particular point locations? For example, HT7 and PC7 are very close to one another on the inner wrist surface — does something about their position make them particularly relevant to emotional stability, a common application of both? Could cells at these positions store specialized information, or might they release their information into a local environment that has special sensitivity, or could a combination of these possibilities be in play? And how do different meridians link up into a larger network? Researchers who study acupuncture are in an exciting time. Work continues on understanding the whole organism response to treatment, even as approaches using cultured cells are becoming more productive and targeted. Along this experimental continuum, I hope that partnerships between researchers and practitioners will be naturally enriched, for the benefit of us all.
Langevin HM, Churchill DL, Cipolla MJ. Mechanical signaling through connective tissue: a mechanism for the therapeutic effect of acupuncture. FASEB J. 2001 Oct;15(12):2275-82.
Bonten EJ, Annunziata I, d'Azzo A. Lysosomal multienzyme complex: pros and cons of working together. Cell Mol Life Sci. 2014 Jun;71(11):2017-32.
Jaiswal JK, Andrews NW, Simon SM. Membrane proximal lysosomes are the major vesicles responsible for calcium-dependent exocytosis in nonsecretory cells. J Cell Biol. 2002 Nov 25;159(4):625-35.
Dr. White-Gilbertson began her professional life as an acupuncturist in 2000 after studying at The Midwest College for Oriental Medicine (then The Midwest College for the Study of Oriental Medicine). In 2002, a long standing interest in possible connections between acupuncture and Western biomedicine led her to formally train in molecular biology. She earned a PhD for her work in chemotherapy resistance and programmed cell death as part of a dual degree program which also granted her a Masters in Clinical Research from the Medical University of South Carolina in 2009. In total, Dr. White-Gilbertson spent 10 years researching cancer biology and now works with cancer databases addressing issues of incidence and outcome for this difficult disease. She lives and works in Charleston, SC.
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