Doctor's Review: Medicine on the Move

October 25, 2021
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From runny noses and sneezing to itchiness, allergies have been getting under our skin for millennia

Did you know that the lowly strawberry is responsible for a major historical event? It's true. Though England's King Richard III (1452-1485) is now famous mostly for his purportedly hunched back, tyrannical rule and subsequent unflattering immortalization by Shakespeare, he may also have been the first to inflict death by dessert.

According to a biography written by Sir Thomas More (1478-1535), Richard was mistrustful of his old friend, Lord William Hastings (1431-1483) — a powerful figure who was sympathetic to the throne's rightful heir, the young Edward V (1470-1483) — and needed to do away with him in order to accede the throne.

Richard, who was allergic to strawberries, secretly ate a few before meetings with Hastings one day. After falling ill quickly and dramatically, he publicly accused Hastings of putting a curse on him. The hapless Hastings was then arrested on charges of treason and dispatched in the first recorded execution at the Tower of London. Richard was coronated a week later.

Millennia before this famous example of assault by anaphylaxis, the man considered by most historians to be Egypt's very first pharaoh, Menes (c. 3100-3000 BCE), allegedly met his mummifier after succumbing to a wasp's sting. Though not many details of the incident are known, the symbol of the bee would be forever included in Menes' hieroglyphic cartouche, and those of his descendants. There is, however, conflicting evidence that Menes was in fact killed by an angry hippopotamus. Regardless, not too long after, Babylonian medical texts refer to two separate cases in which bees or wasps resulted in death. No doubt, all those hanging gardens must have been full of bugs.

Hay Days
Though plain old seasonal allergic rhinitis — the most common of all allergies, some say affecting up to 25 percent of the adult population — may not have the drama or intrigue of anaphylaxis, its appearance in medical literature is significant nonetheless.

The Roman philosopher and poet Lucretius (99-55 BCE) famously noted in his poem "On the Nature of Things," that "What is food to one man may be fierce poison to others." Hippocrates also had an inkling about allergies, noting that for some folks, symptoms we'd recognize today as allergic reactions came and went with the seasons.

In 1565, an Italian surgeon named Leonardo Botallo (1519-1588) was the first to recognize the connection between some plants and allergic symptoms. The condition he termed "rose fever" could be induced in certain people by forcing them to sniff flowers and caused itching, sneezing and watery eyes. The cure? Bleeding, of course.

A contemporary of Botallo named Pietro Andrea Mattioli (1501-1577) made a similar observation with regards to cats. But it was a British physician who would be the first to formally identify and study an allergy — hay fever — as a distinct medical condition with its own set of causes and effects.

After Dr John Bostock (1773-1846) received his degree from Edinburgh Medical School in 1794, he moved to England to set up shop. Soon his area of interest began to lean toward personal matters. Bostock, it turned out, was plagued by what he'd always referred to as his "summer catarrh." In 1819, he published "A Case of Periodical Affection of the Eyes and Chest," the case being his own. Bostock recounted, in excruciating detail, his decades-long seasonal suffering, noting that his symptoms waxed and waned depending on the abundance of greenery each year.


He also experimented with and reported on the traditional treatments of the day. Sadly, the digitalis, mercury, ice baths and cupping offered poor Bostock little relief, though the copious amounts of opium may have helped in other regards.

Over nearly a decade, Bostock tried to find other sufferers to further his research. He could only come up with 28 cases besides his own — and it took him nearly a decade to find even these. But they provided enough insight for him to publish another study in 1828, in which he referred to the disease as "hay fever" for the first time after realizing that haying season seemed to be the time when symptoms were at their worst. He might as well have called it ice-cream fever, since we now know hay has nothing to do with allergic rhinitis, though neither does fever, for that matter.

A few decades later, Manchester physician Charles Blackley was the first to prove what a few had suspected it, that Bostock's hay fever was in fact triggered by plant pollen. Like Bostock, Blackley was himself a sufferer, and over 14 long years spent using himself as a pin-cushion personally ingesting and applying dry and fresh pollen to all of his orifices and surfaces in every possible way. His myriad hives proved once and for all that pollen — and not hay — was to blame for the condition.

He published his results in 1873 and thoughtfully advised his patients to summer on their yachts instead of at their country estates. Alas, the medical community was happier to attribute allergies to the burgeoning germ theory, and so seasonal sufferers sniffed and oozed on in miserable solidarity.

Anaphylactic Docs
An understanding of more serious allergies came to the fore in 1902 when an aristocrat's curiosity about jellyfish stings led to a chance discovery. Unlike most of today's scandal-plagued, bed-hopping royals, Prince Albert I of Monaco (1848-1922) had a sincere interest in something substantial — oceanography.

One day, he invited a pair of French physiologists, Charles Richet (1850-1935) and Paul Portier (1866-1962), for a sail on his yacht to study the Portuguese Man O' War. Their aim was to isolate its toxin and use it to inoculate dogs, hoping to provide protection — or "prophylaxis" — against further stings, ultimately making the ocean a safer place for people to swim. It worked with smallpox, so why not venom?

To their consternation, after the dogs were exposed to the initial dose, the further injections designed to ensure their immunity — no matter how small were — induced a far more serious reaction. Within minutes, the dogs were dead, following the sudden and dramatic onset of vomiting, diarrhea, swelling and asphyxia.

After studying this extreme sensitivity to certain proteins and determining that the anaphylactic state could only be induced following an incubation period of several weeks after the initial introduction of the toxin, Richet and Portier termed the reaction "anaphylaxis," meaning "against protection."

The term "allergy" itself — a combination of the two Greek words for "altered responses" — first came into use shortly after, coined by Clemens Peter von Pirquet (1874-1929), an Austrian pediatrician working as head of pediatrics at Johns Hopkins Hospital in 1906. He used the catch-all phrase to refer to the process by which ordinarily benign substances cause unlikely, unpleasant and often extreme responses in certain highly sensitive individuals. At last, the problem finally came into its own, opening the door to serious consideration by the scientific community, which, ultimately, led to the search for causes and treatments.

Allergy sufferers everywhere wheezed a sigh of relief when the Nobel-prize-winning Italian pharmacologist Daniel Bovet (1907-1992) came up with the first antihistamine in 1937. Just over a decade later, two other Nobel laureates, American physician Philip Hench (1896-1965) and chemist Edward Kendall (1886-1972), added to their relief with the introduction of corticosteroids.

Along with the immunotherapy injections devised by English physician Leonard Noon in 1911, antihistamines and steroids remain pretty much the only treatment options for allergy sufferers, though some promising insight into the nature of the condition means hope for a cure is on the horizon. Until then, EpiPens and a hearty gesundheit will just have to do.


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