In 1999, Duane Graveline’s doctor prescribed him Lipitor, a drug that was supposed to decrease the Apollo astronaut’s cholesterol levels. Instead, it caused him to forget he was married. Fortunately, the amnesia was rectified once his body metabolized the Lipitor (Westphal). While Duane Graveline’s experience with the unintended side effects of a modern pharmaceutical did not have lasting effects on his well being, thousands of other patients have not fared so well. According to a U.S. Department of Health study, adverse drug effects are responsible for 700,000 emergency room visits and 100,000 hospital admittances every year (“Medication Errors”). Adverse drug reactions comprise 2.5% of all emergency room visits for accidental injuries and 6.7% of emergency room visits that lead to hospitalization (Budnitz). This financial and practical strain on hospitals only adds to American expenditures on pharmaceuticals, which continue to grow annually. In 2014 alone, Americans spent nearly $374 billion on prescription medication (Sifferlin). The obvious deficiencies of conventional drugs present medical science with a dilemma: Could there be a safe, effective, and cost-efficient way to lessen our dependency on pharmaceuticals?
New breakthroughs in the field of bioelectronics might provide an answer to this question. About fifty years ago, doctors began using electrical stimulation devices to manipulate body systems that operate on electrical impulses. Electrical treatments have evolved dramatically from the implantation of the first pacemaker to the implantation of the first bioelectronic nerve stimulator. However, the field must surmount several more hurdles before electrical intervention can replace pharmaceutical drugs. This essay will trace the history of electrical interventions in the body, from its beginnings in the invention of the pacemaker to the problems bioelectronic devices currently face as a treatment for autoimmune disorders. If these problems are addressed through interdisciplinary collaboration and additional funding, bioelectronic medicine will become an even stronger alternative to pharmaceuticals as an economical and effective treatment for chronic autoimmune disorders.
Prior to the mid-twentieth century, the only treatment for heart disease was lifelong bed rest. So lacking was the availability of treatment options to patients with cardiac disorders that, in 1915, a group of concerned doctors and philanthropists formed the Association for the Prevention and Relief of Heart Disease, an organization that would eventually be renamed The American Heart Association (“History of the American Heart Association”). The absence of a sufficient pharmaceutical solution precipitated the need for a novel kind of approach. In 1950, the advent of electric medicine was realized by an assistant professor of electrical engineering in an upstate New York barn. While tinkering with circuits and resistors, Wilson Greatbatch noticed the electric pulses emitted by his faulty heart rhythm recording device mimicked the beats of a human heart. Realizing the possibility of electricity as an alternative treatment for heart disease, Greatbatch studied ways doctors could correct dangerous arrhythmias without the use of medication. In 1958, he designed the first implantable pacemaker (Feder).
Over twenty years later, doctors began testing another form of electrical intervention in the body to treat Parkinson’s disease, a neurological condition. Less than a century and a half after Parkinson’s disease was identified, doctors found that destroying parts of the brain associated with motor control could ameliorate the symptoms of the disorder. Not surprisingly, “lesioning” sometimes caused irreversible side effects more debilitating than Parkinson’s itself (Clements). In the 1970s, scientists proposed a pharmaceutical alternative, Levodopa. Some years after Levodopa was first prescribed, doctors discovered that their patients’ brains were becoming resistant to the drug. Once this happened, patients would experience exacerbated Parkinson’s symptoms (Clements). After the failure of both surgical and pharmaceutical treatments, scientists searched for alternatives. In the late 1980s, they found their answer in the form of deep brain stimulation (DBS). By delivering an electric pulse to the parts of the brain associated with motor control, doctors could imitate the effects of “lesioning” without the problem of irreversible side effects (Clements). The discovery of DBS was a milestone in the legacy of electrical treatments because it was the first electrical intervention of the brain, the control center of the nervous system.
The use of targeted nerve stimulation as a treatment for rheumatoid arthritis was another such milestone. While the electric pulses DBS delivers are limited to the brain, targeted nerve stimulation alters the communications between neurons throughout the rest of the body. The nervous system innervates every organ in the human body, and the electrical pulses exchanged between neurons govern the behavior of these organs. By stimulating or inhibiting the exchange of the pulses, scientists found they could regulate biological functions and cure diseases (Famm). Rheumatoid arthritis is a debilitating disorder characterized by severe swelling of the joints, in part caused by an excess amount of circulating tumor necrosis factor (TNF), an inflammation-causing cytokine. This disease is often treated with TNF blockers and steroids, whose long-term use can lead to side effects such as weight gain, bone disorders, and diabetes (“Rheumatoid Arthritis”). These pharmaceuticals not only inhibit the inflammatory response in the joints, but also throughout the entire body. This makes a patient much more susceptible to opportunistic infections (Bingham). In 2002, researchers discovered that signals transmitted through the vagus nerve control TNF production, and that altering the signal by electrically stimulating the vagus nerve can inhibit the production of TNF in the liver, spleen, and kidneys of mammals with inflammatory disease (Tracey). In patients with rheumatoid arthritis, the neural signal controlling production of TNF is faulty, leading to excessive inflammation in the joints. Restoring the correct signal by stimulating the vagus nerve mitigates the swelling, while also allowing for the production of the TNF necessary to induce healthy immune responses (Andersson). Instead of utilizing a drug to negate the effects of inflammation-causing cytokines, vagus nerve stimulation simply inhibits the natural production of excess TNF in patients with inflammatory disorders. Vagus nerve stimulation mimics the beneficial effects of anti-inflammatory drugs without the long-term expense and side effects.
Though bioelectronic medicine has evolved considerably in a short amount of time, researchers and doctors must still address significant problems with the current technology. In a Nature article, a group of bioelectronics researchers outlined the problems they hope to address. Neural tissues with different functions are often woven into the same nerve bundle. Electrical impulses must be transmitted through a very specific series of nerves to produce the intended biological response. Stimulators are not yet sufficiently precise to target specific areas of tissue within a nerve bundle. In addition, neural circuits run on very specific communications between certain nerve cells. Electric impulses, called action potentials, must fire in a precise pattern for a specific neural pathway to function properly. Current modes of nerve stimulation present problems. First, they are unable to reliably target specific cells. In addition, the impulse frequencies required to activate particular neural pathways are presently unknown, making many of these devices too imprecise to be used in a clinical setting (Famm). Imprecise intervention can be extremely dangerous in certain situations. For instance, nerve stimulation has been proposed as a method to treat obesity. A study had found that stimulating agouti-related peptide neurons in mice increases their eating habits. Logically, preventing these neurons from firing seems like a viable treatment for obesity. However, doing so results in anorexia (Aponte; Famm). Such is the problem with current nerve stimulating technology—circuits may be activated or deactivated, but there is no way to finely regulate them.
To solve this problem, scientists must determine the exact frequency of action potential firing that will produce a certain response for each disease before nerve stimulators can be used to treat them (Famm). Such an endeavor would require millions of dollars in research. Unfortunately, private donors rarely fund such projects, as medical research often requires large startup costs with no immediate payback. Public funding is a critical component of medical progress, yet the U.S. government has been progressively allocating less money to biomedical research over the years. In 2013, the grant application success rate fell to a record low of 16.8% (Boadi). Fortunately, bioelectronic research has recently received funding from some unexpected sources. Pharmaceutical companies, which have historically profited from the continual use of drugs by patients with chronic illnesses, stand to potentially suffer major financial losses with the partial replacement of pharmacological treatments with electrical ones. A major international pharmaceutical company, however, recognizes a possible avenue for profit in the manufacture of neurostimulators. GlaxoSmithKline (GSK) has offered a one-million-dollar reward for the first scientist to build a neurostimulator that utilizes a closed feedback loop to read and modulate nerve signals. Additionally, GSK has invested millions in outside bioelectronic laboratories to develop such a device. This stimulator would interpret, analyze, and correct faulty neural signals to cure and prevent disease (“Bioelectronics R&D”). Creating such a device seems all the more likely with recent advancements in nanotechnology (Famm). While funding from private sources has certainly contributed to the advancement of bioelectronics, large amounts of public funds are necessary to facilitate more effective collaborations between neuroscientists, biomedical researchers, and electrical engineers.
As knowledge of the relationship between electricity and biological functions expanded, so have the ways in which doctors use electricity in place of pharmaceutical and surgical intervention. Doctors now use deep brain stimulation to alleviate the symptoms of Parkinson’s and targeted nerve stimulation to treat disorders. Each advancement pushes medical science closer to a time when medications can be replaced with neurostimulators that induce or preclude the body’s natural production of pharmacologic agents. While bioelectronic technology is still in its infancy, biostimulators have the potential to alter biological responses to treat disease more safely, effectively, and cost-efficiently. Without proper funding towards the development of such technology, however, the prognosis of American healthcare, with respect to bioelectronics, will remain uncertain.
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