A couple weeks ago an ER physician, Dr. Richard Levitan, wrote an opinion piece in the NY Times about how a simple blood oximeter can give an easy and early warning about possible coronavirus infection. The key issue being that in his experience, many COVID-19 patients showed unbelievably and even lethally low blood oxygen readings but did not show any of the expected signs of severe hypoxia such as unconsciousness or at least desperate gasping for breath. They were, as he said, just checking their cellphones as if nothing were wrong.
After reading that article I immediately placed an order on my Amazon Prime account for a cheap well reviewed oximeter. It turns out I was not the only one as Slate reported that oximeters were sold out at pharmacies and on Amazon after Levitan’s article.
Amazon’s next-day shipping was one of the casualties of COVID-19 – the checkout page showed that the expected delivery for my new purchase was two weeks out. Amazon had spoiled me over the past year with their next-day or even same-day deliveries so two weeks felt like next year. While I waited for my pulse oximeter, I started wondering about how we learned to measure our blood…
In a way it started with Marcus Aurelius, Emperor of Rome from 161-180AD. General. Conqueror. Persecutor of Christians. Writer of The Meditations (which is still read today especially by those who appreciate Marcus’s stoic philosophy – perhaps appropriate again in today’s pandemic lock-down).
One of the most devastating events of Aurelius’s career was the Antonine Plague (Antoninus was his family name: Marcus Aurelius Antoninus Augustus). The plague, possibly smallpox, broke out around 165AD and is estimated to have killed about 5 million people throughout the Roman Empire (approximately 10%), including the Emperor(s)... and is implicated in the empire's decline and fall.
On the ground among the Roman troops and citizens being decimated by the plague was the outstanding physician/scientist of the ancient world, Galen. Decimated, by the way, is derived from the Roman word decimatio, which was a form of military punishment in which every tenth man was executed when a group was guilty of a capital offense such as cowardice or desertion.
Galen was summoned by Marcus upon the outbreak of the plague to be personal physician to both Marcus and his co-Emperor, Lucius Verus, during their campaign into what is now Germany. Galen was spared from having to go campaigning among the Germanic barbarians, but stayed behind to care for Commodus, heir to the Imperial throne. Galen witnessed the plague among the Roman citizens as well as among the troops stationed in Aquileia, and his descriptions of the symptoms have been so important to medical history that the Antonine Plague was also known as the Plague of Galen (not an attribution I would value).
Galen was born in 129AD in Pergamon (Bergama in modern day Turkey) to wealthy Greek parents. His father, Aelius Nicon, spared no expense on his son’s education. When Galen was 16 his father sent him to study medicine. Nicon died in 148, leaving his wealth to a 19-year-old Galen who subsequently travelled and studied at some of the best medical centers of the time, eventually ending up at the best school of them all in Alexandria.
When Galen was 28 he finally returned to Pergamon. According to his own writings Galen became physician to the gladiators belonging to the High Priest of Asia by a dramatic dare he posed to the incumbent physicians. He disemboweled an ape and challenged the others to repair the damage - but none took him up. So Galen did the surgery himself, and thus won his position. Only a couple gladiators died during Galen’s tenure, compared to sixty who died under the care of his predecessor. Importantly, Galen took advantage of the open wounds likely suffered by the gladiators to study the inner workings of the human anatomy, since dissection and vivisection of human bodies was prohibited. He also experimented on animals, mostly pigs and monkeys, to develop his understanding of human physiology.
By the time Galen accepted Marcus’s invitation to be the court physician, he was about 40 years old and had spent his adult life since his teenage years carefully observing his patients and experimenting on animals in order to better understand how the body worked - so he could be a better physician. Now in Rome at the Emperor’s bidding and at the height of influence, he began writing so prodigiously using an army of scribes that Galen’s works comprise over half of the ancient writings that have survived to this day. The known works of Galen are thought to be only a third of his total body of work.
One of the many subjects he wrote about was circulation. At the time, medicine was dominated by ancient ideas of the four humors: blood, phlegm, yellow and black bile. These humors were thought to be in balance during good health, and out of balance during poor health. Many treatments were predicated on bringing these humors back into balance - for example an excess of blood (sanguine) required blood-letting such as with leeches - a practice that lasted thousands of years into the 1800s. Circulation was thought at the time to involve air from the lungs pushing blood through the left side of the heart and through the aorta. Galen used dissection to prove that arteries carried no air - nothing but blood. He was the first to demonstrate that there were two parts to the circulatory system, a darker venous system and a brighter arterial system.
Galen’s works were a major leap in advancement from where ancient medicine and anatomy were at the time. His works were so revered that they literally stood the test of time - but unfortunately the key aspect of his philosophy which he embraced throughout his career was lost to over a millennium of subsequent physicians and scientists - that of using direct observation and experiments to learn. Most physicians who followed him unfortunately learned by rote and were merely book-smart – smart on Galen’s books…
There were major errors in Galen’s books.
For example, Galen believed that blood that entered the right side of the heart permeated the septum (separating the ventricles) via invisible pores to reach the left side of the heart. The two systems of venous and arterial flow that Galen discovered were, he believed, two separate systems that only connected through invisible pores. He believed the arterial flow originated in the heart to dissipate heat, and that the venous flow originated in the liver.
It was not until a thousand years after Galen, around the early 1200’s, that Arabic physician Ibn al-Nafis directly challenged Galen’s claims of pores in the septum separating right from left ventricles. Al-Nafis discovered, using Galen’s own methods of dissection and experimentation, the details of pulmonary circulation which eluded Galen. Galen would have been proud. Al-Nafis correctly showed that dark venous blood left the right ventricle, went through the pulmonary artery to the lungs, was infused with air and turned bright red, then passed through the pulmonary vein into the left ventricle. He also correctly deduced coronary and capillary circulation, and corrected Galen’s errors to show that the heart was the source of the pulse, among many other important anatomical and physiological discoveries…
Andreas Vesalius, a professor of anatomy at Padua University in Italy, was the first Westerner to challenge Galen in the 1500s. Galen’s works continued to be revered uncritically by the Catholic Church and thus the rest of the medical and scientific community in Europe. A couple Spanish and Italian scientists, contemporary with Vesalius, began to propose the correct linkage of venous and arterial circulation through the pulmonary system. Unfortunately, outside of the Arabic world, Galen’s teachings continued to predominate until William Harvey in the 1600’s. Harvey rigorously applied Galen’s experimental methods and became the first in the Western world to fully and correctly describe the circulatory system (at least within the limits of the technology available to him at the time – for example, he could not observe and did not predict the presence of capillaries connecting outgoing arterial blood flow to the venous return).
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Harvey’s father was a mayor with good family connections, which enabled his son to access some of the best education at the time, including in Cambridge where he got his Bachelor degree, and then after some travelling in continental Europe, he entered the University of Padua in Italy. After getting his Doctor of Medicine degree at Padua, he returned immediately to England to get his Doctor of Medicine from the University of Cambridge. He eventually became personal physician to King James I (is this story sounding familiar?).
Decades of observation and rigorous experiments led Harvey to his 1628 book De Motu Cordis (Anatomical Account of the Motion of the Heart and Blood) for which he is credited with being the first Western physician who correctly detailed the function of the heart and circulatory system, breaking decidedly with Galen, whose errors on circulation were still vigorously defended by Harvey’s peers…
A year before Harvey published his De Motu Cordis in 1628, Robert Boyle was born the fourteenth child of the First Earl of Cork at Lismore Castle. Boyle also had the advantages of excellent education and traveled through continental Europe as a young man, even spending time in Florence during Galileo Galilei’s final years. When young Boyle returned to England, he was determined to pursue scientific research. He succeeded to such an extent that he is considered to be the father of modern chemistry. We have him to thank for Boyle’s Law, for example, which established the inverse proportionality between pressure and volume of a gas. And among many other observations, Boyle is the scientist who proved that air is necessary for combustion – and for life – by using an efficient vacuum pump of his own design. By removing air from a bell jar, he observed that a burning candle – and a mouse – were both extinguished in the absence of air.
But it was John Mayow, a contemporary of Boyle’s and a chemist and physician, who demonstrated that there was an active and inactive fraction of air responsible for that combustion and life. He correctly deduced that the active fraction of air which he called spiritus nitro-aereus comprised a fifth part of air. Today we know oxygen is 20% of air, confirming Mayow’s results from the mid-17th century. Mayow also correctly proposed that the lungs separated the active component from air and passed it to the blood.
It was not until 1774 that British clergyman Joseph Priestly isolated oxygen by thermal decomposition of mercuric oxide, and demonstrated that this isolated fraction was sufficient for combustion and life (again using candles and those unfortunate mice for subjects). Although Priestly is given precedence for his discovery of the life-giving molecule, the name comes from French chemist Antoine Lavoisier who conducted independent experiments on the same “vital air” that Priestly worked on. Lavoisier named it oxygen for his mistaken notion that this gas was the key constituent in acids. Despite this error, Charles Darwin’s grandfather Erasmus Darwin popularized the name in a poem titled Oxygen in his very popular book The Botanic Garden, and Lavoisier's name has stuck…
Then it was Friedrich Ludwig Hunefeld working in Leipzig in 1840 who was the first to discover hemoglobin in dried worm’s blood and showed that hemoglobin bound to oxygen. The reversibility of hemoglobin’s oxygen-binding property was described a decade later by Felix
Hoppe-Seyler who is described as the founder of modern biochemistry. This observation showed how hemoglobin in red blood cells could take up oxygen in the lungs but then release it to the tissues where it was needed. Importantly, Hoppe-Seyler was also the first to describe the absorption spectrum of hemoglobin in 1862 using a spectroscope, and to show that oxygenated hemoglobin absorbed light differently from deoxygenated blood.
The spectroscope that Hoppe-Seyler used on hemoglobin was invented in 1860 by Robert Bunsen (who invented the Bunsen burner) and Gustav Kirchhoff (who developed Kirchhoff's circuit laws still used today). Bunsen invented his burner as a means to identify metals and salts by the colored flame they gave off. It was Kirchhoff who suggested using a prism (first used by Isaac Newton in 1666 to separate white sunlight into constituent colors) to separate out the colors so similarly colored flames could be further distinguished. Their spectroscope revolutionized analytical chemistry and biochemistry and led the way into non-invasive blood analysis.
About this same time, we also had a German physiologist Karl von Vierordt who developed many tools and techniques for measuring blood circulation, such as a hemotachometer to measure the velocity of blood flow, and an early form of today’s sphygmomanometer to measure blood pressure. But one of the innovations he is not well known for, because it was well ahead of its time, was to use the Bunsen-Kirchhoff spectroscope to measure blood oxygenation and the consumption of oxygen in tissues. He did this in 1876.
The first clinical development of a light-based instrument to measure blood oxygenation was not until 1935 by German physician Karl Matthes, almost 70 years after Vierordt’s first use of a spectroscope in a research setting. Matthes and his collaborator Franz Gross first reported the use of a red and infrared light in an oxygen saturation meter in 1939, and this is fundamentally (with many, many engineering improvements) the forerunner of today’s oximeters…
I was ecstatic when my oximeter was delivered within 4 days of my order instead of 2 weeks.
I put two AAA batteries (included for Amazon’s bargain price of $34.99) into the oximeter, and pushed the on button to see the little red LED lights blink sleepily on. This little pulse oximeter is designed like one of those black triangular paper binder clips, you know, where you pinch the two nickel-plated wire arms and the black sheet metal clip opens like a mouth and bites down on the sheaf of papers you signed for your mortgage application… instead of paper this oximeter clip bites down on your finger. Gently. No blood.
Red LED lights flashed for a few seconds and then reported “%SpO2 95” and “♥/Min 68”. I guessed that it was telling me something like my blood oxygen level was 95%. But was that good, was that bad, did I have COVID-19?
I checked the kids and their pulse was higher than mine as expected, and their %SpO2 reading was in the 99-100% range. I checked the wife and her readings were similar to the kids. Huh. Why was mine 95%? I then googled what was the expected blood oxygen range, and found that between 95 to 100 is normal. Huh. So then, I’m at the low end of the normal range – is that because I’m rapidly declining and about to fall into the abnormally low range caused by COVID-19, or have I always been on the low end of this measurement, or is it because I once had that youthful 100% reading but I’m now a middle aged duuude on the downhill slide to decrepitude…
Having a device and the data it reports is not enough to assuage the neuroses and questions that COVID-19 causes. Buyer beware. ;)
And here is a list of the references I thought were most helpful from my googling:
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