Jose L Vega, Department of Neuroscience and Stroke, Novant Health, Forsyth Medical Center, North Carolina, USA
A few years ago, after a stressful day at work, I found myself glued to a television news segment about freediving, which inspired a personal journey from the ocean, through historical archives, and into the heart of a fascinating medical enigma. The news segment, titled Death-defying free dives, featured a man who could plunge over 100 metres into the ocean and return to the surface, unassisted, on a single breath of air. As a neurologist who had often witnessed the devastating effects of even brief episodes of respiratory arrest on the brain, I wondered how he managed to remain unharmed by his extreme diving. But what really puzzled and even captivated me was the paradoxical tranquility he emanated during his risky dives.
Later that year I decided to enroll in a recreational weekend-long freediving course in which I learned about the mammalian dive response (MDR), a collection of oxygen-conserving reflexes that allows aquatic air-breathing mammals, like dolphins and whales, to remain submerged for extended periods of time. These reflexes 1) slow down the heart rate (i.e. diving bradycardia), 2) shunt a large portion of the body’s blood volume towards the lungs (i.e. the blood shift), and 3) release splenic red blood cells into the systemic circulation (i.e. the splenic contraction) (Panneton, 2013). Although I found this to be a fascinating biological response, I questioned why it was relevant to the course; after all, humans are not aquatic mammals. But then the instructor unleashed a bewildering revelation: humans also possess this response. I was fascinated, yet alarmed. This was the most robust set of neurological reflexes I knew, and yet I had stumbled upon it fortuitously at a recreational freediving course. Why wasn’t the MDR part of the formal medical curriculum?
The following day, we practised the actual mechanics of freediving at a local Olympic diving pool. Unlike the other students, who were excited to freedive, I was mostly excited to experiment with my newly discovered MDR. During one of my dives I stayed at the bottom of the pool long enough to test my diving bradycardia reflex by aligning my index and middle fingers over my radial artery. Within thirty seconds, I witnessed my pulse dwindle from 60 beats per minute to 12. I then felt a mixture of fear and euphoria; I had only seen such dismally low pulses in unconscious patients going into cardiac arrest. Yet, there I was, enwrapped by the tranquility of submersion, counting from one to five between heart beats.
After the course was over, I adopted freediving as a hobby, and decided to learn as much as I could about the human MDR. Unfortunately, this simple goal turned out to be much more difficult than I expected because, compared with other species, the number of human MDR studies was minuscule. The majority of them pertained to the exercise physiology of professional freediving, but some–written in the second half of the twentieth century–exclusively addressed the therapeutic implications of “the diving reflex,” (Wildenthal et al., 1975), as diving bradycardia is known to physicians. This curious treatment strategy involved controlling frantic heart rhythms by immersing patients’ faces into buckets full of water. While, its impractical nature led it to be dropped from routine medical practice, the diving reflex’s fascinating physiology earned it a permanent place in the medical curriculum. However, it did so in isolation of the rest of its parent response, the MDR. Since then, aspiring physicians are taught about the diving reflex, but not about the MDR.
As I continued to scour articles for human MDR literature, I noticed that their introductions occasionally included historical morsels about Paul Bert (1833–1886) being the “father” of diving bradycardia (Harding et al., 1965). One day, out of sheer serendipity, I picked up an article that discussed the experimental circumstances of his discovery. Bert had set out to compare the survival times of ducks and chickens subjected to forced water immersion (i.e. drowning). About a duck that survived longer than 16 minutes, he wrote: “… the heart, which was beating 100 times per minute before immersion now only gives 14 regular and deep beats” (Foster et al., 1986). This description would later be uniformly embraced as the discovery of diving bradycardia, and as the first evidence of the MDR. But as I read it, I wondered how it illustrated the reflex given that the endpoint of the experiment was death. To show that his observation was a reflex, Bert needed to demonstrate a normalisation of the heart rate in ducks removed from the water while still alive. Without such a demonstration, the duck’s slowing heart rate could simply reflect its natural progression towards death. Curious, I enlisted a French-speaking colleague to review Bert’s original publication and learned that none of his ducks survived. More importantly, his celebrated quote turned out to be a singular remark, detached from his methods and conclusions (Bert, 1870).
The following year, while freediving in Dahab, I surfaced from a dive feeling uncharacteristically tired and decided to rest for the remainder of the day. Walking back to my hotel, I also felt congested and short of breath, as if I had suddenly developed a severe cold. My symptoms reminded me of Nick Mevoli, a fellow freediver who had died in 2013 while attempting to set a U.S. record in the Bahamas. Nick’s was the first competition-related death in the entire history of the sport. His autopsy revealed a frothy residue and frank blood inside his alveoli, which suggested that high pressure within the pulmonary blood vessels had caused him to drown in his own fluids and blood. Suspecting I could be suffering from a mild version of such a deadly process, I decided to suspend freediving for a few weeks and spend my remaining time in Dahab relaxing, reading, and enjoying the awe-inspiring scenery.
One afternoon, while contemplating the Arabian Desert across the Red Sea from my favourite café, a question suddenly popped into my head: if Bert was not the father of diving bradycardia, then who was? I figured that the best place to start looking for this answer was in Bert’s own background literature. Three espressos and one bottle of water later, I had read through a doctoral dissertation originally published in 1786 titled “The connection of life with respiration,” (Goodwyn, 1788), which was cited in Bert’s original text (Bert, 1870). This ancient document was freely available on the Internet and contained a clear and complete description of diving bradycardia (Goodwyn, 1788). In it, the author – Edmund Goodwyn (1756–1832) – showed for the first time that forced water immersion, and other forms of suffocation, caused death by preventing dephlogisticated air (i.e. oxygen) from entering the bloodstream (Vega, 2018a). One experiment described the gradual deceleration of a toad’s heart rate during forced immersion, until it came to a halt. Thinking the toad had died, he removed it from the water, where moments later it took a few breaths, normalised its heart rate, and began walking about “without any expressions of uneasiness.” Goodwyn then repeated the experiment in the same unfortunate toad, and in other animals, noting that “in all examples the contractions of the heart were diminished in frequency” (Goodwyn, 1788). Thus, my serpentine journey through the MDR literature had amounted to a diving bradycardia paternity test which pointed to Goodwyn as the reflex’s new father (Vega, 2017).
When I finally arrived home from my trip, a small pile of miscellaneous envelopes and medical publications awaited in my mailbox. One of the journals in it contained an article about an unfamiliar neurologic mystery: the sudden and unexpected deaths of epileptic patients (SUDEP) (Devinsky et al., 2016). Up until then, neurologists had considered seizure-related deaths to be rare, but a much higher frequency of such deaths was beginning to surface in the epidemiological literature, especially among patients who suffered from uncontrolled convulsive seizures. The typical SUDEP case involved a young and healthy victim who convulsed during her sleep, and was found dead in the morning, in bed. Witnessed cases invariably involved one or more convulsions during which victims ceased to breathe for prolonged periods of time before their hearts slowed to a halt. Mysteriously, autopsy reports were normal, with one salient exception: more often than not, their lungs demonstrated acute pulmonary oedema and pulmonary haemorrhage (Terrence et al., 1981).
Still influenced by my recent experiences with freediving, I could not help but wonder whether these autopsy findings might stem from the same process that took Nick Mevoli. After all, both Nick and SUDEP victims ceased to breathe for prolonged periods of time before they died: Nick while diving, and SUDEP victims while convulsing. I quickly realised that these physiological conditions might relate back to the three reflexes of the MDR, and to the blood shift in particular, as excess blood in the lungs could increase the pressure inside the pulmonary blood vessels and cause pulmonary oedema and pulmonary haemorrhage. I tried to discuss this notion with other neurologists but I invariably lost their attention at the word “pulmonary”. After some time and a great deal of thought I decided to propose a mechanistic hypothesis to investigate a possible role for the MDR in SUDEP (Vega, 2018b).
The outcome of my retrospective reading exemplifies a notable, yet rarely discussed aspect of science history. Goodwyn’s thesis remained in obscurity for almost a century before it finally helped Bert advance the very line of research that gave us the MDR. In turn, the human side of this robust physiological response has escaped the attention of physicians for decades, despite its potential role in medical conditions like SUDEP. It seems, therefore, that the history of science holds much more than engaging anecdotes with which to embellish the introductions to our manuscripts. At its very core it holds illuminating concepts that can further our investigational pursuits and, with a little luck, provide the missing pieces to our scientific puzzles.
Bert P (1870). Leçons sur la physiologie comparée de la respiration. Paris : J.B. Baillière; Londres: Hippolyte Baillière.
Devinsky O et al. (2016). Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Lancet Neurol 15, 1075–1088.
Foster NK et al. (1986). Leukocytosis of exercise: role of cardiac output and catecholamines. J Appl Physiol (1985) 61, 2218–2223.
Goodwyn E (1788). The connexion of life with respiration, London, T. Spillsbury.
Harding PE et al. (1965). Diving bradycardia in man. J Physiol 181, 401–409.
Panneton WM (2013). The mammalian diving response: an enigmatic reflex to preserve life? Physiology (Bethesda) 28, 284–297.
Terrence CF et al. (1981). Neurogenic pulmonary edema in unexpected, unexplained death of epileptic patients. Ann Neurol 9, 458–464.
Vega JL (2017). Edmund Goodwyn and the first description of diving bradycardia. J Appl Physiol (1985) 123, 275–277.
Vega JL (2018a). The Connection of Life with Respiration: Edmund Goodwyn’s unexplored treasure of cardiopulmonary physiology. J Appl Physiol (1985) 125, 1128–1130.
Vega JL (2018b). Ictal mammalian dive response: A likely cause of sudden unexpected death in epilepsy. Front Neurol 9, 677.
Wildenthal K et al. (1975). The diving reflex used to treat paroxysmal atrial tachycardia. Lancet 1, 12–14.