Happy 200th Birthday, Gregor Mendel and Louis Pasteur

December 27 marks the 200th birthday of Louis Pasteur (1822-1895), the scientist who advanced microbiology and vaccinology and was a main figure bringing germ theory to the forefront of medicine. Earlier in the year, July 20, we also celebrated the 200th birthday of Gregor Mendel (1822-1884), whose contribution — genetics — went unnoticed in his time but is central to modern medicine. (Let's leave aside allegations that the Moravian monk played a bit loose with his data.)

During the century in which these men lived, medicine underwent a complete transformation. Once rooted in the ancient Greek philosophy centered on the four bodily humors, it became a science-based system in which physicians diagnosed and treated conditions through an increasingly sophisticated understanding of body tissues and mechanisms.

The most profound part of this shift occurred in the second half of the 19th century with the adoption of germ theory as well as the idea, advocated by Rudolf Virchow (1821-1902), that disease resulted from pathology of certain cells in the body. Ironically, Virchow rejected germ theory and instead thought tissues, which were diseased on account of their cells, simply attracted germs. Believing poverty and other social factors to be the root cells and tissues getting sick, Virchow similarly rejected Darwinian evolution on the basis of an idea that it justified social Darwinism: The idea that survival of the fittest should be applied purposefully to society to allow the wealthy to succeed at the expense of the poor.

Although the ideas of Virchow, Pasteur, and a handful of other researchers in the 1800s would together transform medicine, seeds of doubt about the four humors were already sprouting in the final years of the previous century.

You would notice those seeds if you were you to time travel into the midst of a late-18th-century health crisis, like the yellow fever outbreak that hit Philadelphia in late autumn of 1793. Then the nation's capital and most populous urban center, Philadelphia was sharply divided over a medical issue with strong political undertones — not unlike the politicized reactions to the COVID-19 pandemic of our own era. In place of extremists on one side of the political aisle refusing effective, safe vaccines and those on the other side wearing N95 respirators while jogging outdoors completely alone, however, were partisans for two divergent therapeutic approaches yellow fever.

Knowledge of the viral nature of the fever and its delivery by the Aedes aegypti mosquito still lay more a century into the future. Yet, that ignorance did not stop physicians themselves from dividing into two camps. Members of each group administered and promoted one of two treatment strategies that aligned with their support for either the Federalist Party or the Democratic-Republican Party. But one of the treatments, the one advocated by French physician Jean Devèze and also by the Federalist leader Alexander Hamilton, was better than the other. The main advantage of the so-called French treatment, was that it provided febrile patients with much-needed fluids. Another plus: The alternative was in many cases worse than yellow fever itself.

Which brings us back to the four humors: blood, phlegm, black bile, and yellow bile. Disease was thought to result from an imbalance between these substances. Nowhere in this conception was there room for Pasteur's microorganisms, to which modern medicine homes with antimicrobial drugs, or for the Mendelian genetic factors that we understand and manipulate today at the molecular level.

Still, the old Greek idea was more nuanced than it might seem. The humors were associated with the four elements of Empedocles (popularized by Aristotle): air, fire, earth, and water as well as with the four seasons. Rather than confronting the symptoms of illness, treatment was aimed at restoring balance in the humors. Often, that meant removing blood as well as releasing other fluids through diarrhea and vomiting, typically by ingestion of mercury-laden agents that we now know to be quite toxic.

In 1793, opponents of Devèze and his theory believed that both bloodletting and purgation were required to defeat yellow fever. The leading figure pushing the alternative to the French treatment was Benjamin Rush, the most celebrated American physician of his time. Rush, a devoted Democratic-Republican, emphasized copious bloodletting and administration of purgatives.

Unfortunately, diarrhea and vomiting resulted from these noxious remedies, plus the loss of blood, exacerbated dehydration, electrolyte abnormalities, and hypotension. Yet during the outbreak, many victims desperately accepted Rush's treatments. Those who survived assumed it had been by his hand. Rush himself contracted yellow fever more than once and took his own remedy, which boosted the confidence in his approach.

But in the end, the natural experiment proved Devèze right and Rush wrong. Over the course of several months and then during subsequent outbreaks of yellow fever outbreaks later in the decade, Rush's reputation declined except among his most staunch supporters.

At the time, the Age of Enlightenment had made questioning traditions feel normal and the Industrial Revolution was fostering interest in natural phenomena. Events like the yellow fever outbreaks in Philadelphia helped prime the world of medicine for the advent of germ theory, cellular pathology, and the genetics that would come to define what we now know as healthcare. We should keep this in mind as we wind down the bicentennial year of Mendel and Pasteur.

But we need not dismiss the almost 2000 years of humoral medicine whose final demise those great scientists helped to clinch as pure superstition. Yes, the system looks weird given what we have since come to know about physiology, pathophysiology, biology, biochemistry, and anatomy. Yet, the arrival of the four humor concept represented a significant step forward from the dominant concept of disease: divine intervention. The idea that the body functioned according to a system in which humans could intervene rather than survive at the mercy of arbitrary gods was progressive.

Nor should we discount the idea that people sometimes felt better after a purge or bloodletting. Most of the time, this effect was coincidental and might have happened sooner with no treatment at all. But induced vomiting can be helpful in some situations, such as to remove recently ingested poisons. And removal of blood could have alleviated edema and bought time for patients with congestive heart failure, hypertensive crisis, and other conditions that might improve by decreases in the heart's preload. A few rare cases of hemochromatosis and polycythemia may even have improved from bloodletting.

None of these accidental victories could compete with the mechanistic, pathology-based sort of medicine that began to emerge as our two bicentennial scientists, Pasteur and Mendel, entered their senior years.

Medicine almost certainly would have left the four humors in the rearview mirror long ago but the timing of germ theory in the late 19th century and the rise of genetics to prominence in the 20th century clearly accelerated the transition. As Pasteur said: "Gentlemen, it is the microbes who will have the last word."

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Cite this: Happy 200th Birthday, Gregor Mendel and Louis Pasteur - Medscape - Dec 13, 2022.