We conclude our series covering the book Ancestors of Allergy, edited by F. Estelle R. Simons, MD, FRCPC, with an allergy history timeline of major advancements from the sixteenth through the twentieth century:

• • 1565 Italian-born Frenchman Leonardo Botallo, a well-known anatomist, became the first European to describe the symptoms of seasonal allergy. He described a collection of symptoms headache, sneezing, and an itchy nose among them that developed in the presence of roses. He calls this allergy “rose catarrh.” This observation of nasal symptoms as a reaction to roses was reiterated by scientists throughout the sixteenth century, and the linking of roses to a variety of symptoms caused the designation “rose catarrh” to persist. However, roses were blamed because of their conspicuousness. The actual allergy-inducers were wind-pollinated trees, grasses and weeds now known to be associated with seasonal allergies.
  • Around 1600 Belgian physician Jan Baptista van Helmont describes “summer asthma,” another step toward recognizing seasonal allergies as such.
  • Around 1700 Nehemiah Grew, an English microscopist who focused on plants, began naming various pollen shapes after peppercorns, Holland cheeses, and fish.
  • End of 1700s Seasonal allergic rhinitis was now often observed and recognized. The term “hay fever” replaced “rose cold.” Physicians believed seasonal allergies were an aristocratic disease because it was most commonly diagnosed among the upper class.

• • 1796 Edward Jenner performed his groundbreaking and history altering experiment on James Phipps by inoculating him against smallpox with virulent cowpox matter. Thus, “vaccination,” as Jenner himself called the procedure, was born. For years, medical contemporaries and the public scorned and feared his work, though eventually, of course, he earned recognition.
  • Early 1800s The invention of the stethoscope helps physicians diagnose asthma.
  • 1819 John Bostock of English, who suffered from seasonal allergies since the age of eight, wrote a detailed and classic description of hay fever a description that any allergy sufferer, then or now, could relate to. Bostock, a respected physician, also knew that the symptoms of hay fever could be caused by exposure to other substances, including airborne irritants and odors.
  • 1837-1838 French physiologist Francois Magendie observed anaphylaxis when he realized that rabbits injected with egg albumen often died after a second dose. This began advancements in the field of immunology.
  • Around the mid-1800s American physician Morrill Wyman performed a simple experiment, calling into question the notion that allergic rhinitis was a disease of the privileged classes: He sniffed ragweed pollen to induce an allergy attack. He also posited that the dust and smoke caused by trains were likewise responsible for causing symptoms.

• • 1859 Charles Harrison Blackley, like his contemporaries, initially believed that hay fever was caused by heat, but later amended his view when he noticed that loose pollen from a bunch of grasses collected by his children gave him an allergy attack. He thus pinpointed pollen as the allergen leading to hay fever. Subsequently, he studied as many different types of pollen as he could collect and also examined the distribution of pollen in the environment.Interestingly, as he was learning as much as he could about pollen, he continued experimenting on himself. He rubbed pollen into his eyes and into scratches on his skin (the forerunner of allergy skin tests) and produced an allergic reaction. Blackley’s work garnered much attention, including even a letter from Charles Darwin.
  • 1860 Henry Hyde Salter of England wrote the nineteenth century’s definitive work on asthma, called On Asthma: Its Pathology and Treatment, which summarized everything that was known about asthma at the time. It was considered to be mainly a “nervous disease.” However, Salter also advanced a new theory based on the observation that individuals experienced symptoms when petting a cat, sleeping on a feather pillow, or passing by a poultry shop. Treatments for asthma were still remiss, however. Salter employed coffee, hemp, ether, and the smoke from burning nitre paper or stramonium, an ingredient of “asthma cigarettes.”
  • 1901 Prussian-born bacteriologist Emil Adolf von Behring, considered the “Father of Immunology,” was awarded the Nobel Prize for Physiology or Medicine in recognition of his work with Japanese researcher Shibasaburo Kitasato on serum therapy. The pair studied the passive immune response to tetanus by injecting healthy animals with serum from diseased animals. This is one example of great strides made in the late nineteenth century in the field of immunology and allergic reactions. These laid the foundation for the advancements that developed in the twentieth century.
  • 1902 Based on an experimental induction of hypersensitivity in dogs, Charles R. Richet proposed the term anaphylaxis. Richet and his colleague Paul J. Portier repeatedly observed unexplained sensitization and death of lab animals following a second dose of antigen. Later on, researchers established that anaphylaxis not only occurred after exposure to toxins or venoms, but also to milk, egg whites, and various other animal proteins.
  • 1906 Milton Joseph Rosenau and John F. Anderson began a series of experiments on guinea pigs to study the problem of anaphylactic shock and death following inoculation with diphtheria or tetanus horse serum antitoxins. Their work laid the groundwork for the parameters for antigen-antibody specificity, time intervals between sensitizing and anaphylaxis-inducing inoculations, maternal transmission, and oral sensitization, ultimately reducing inoculation-related morbidity and mortality.

• • 1906 Clemens von Pirquet observed that patients who developed reactions to inoculations and then received a second, smaller dose a few days later often developed asthma or urticaria. Contrary to many who believed that the antigens were becoming more virulent, von Pirquet deduced that the immune system was producing antibodies. In a publication highlighting vaccination, hypersensitivity, prophylaxis, and anaphylaxis, von Pirquet coined the term “allergy.” The same year, Alfred Wolff-Eisner proposed that seasonal allergic rhinitis was a hypersensitive reaction.
  • 1910 German physician Samuel James Meltzer suggested that asthma might be similar to the anaphylaxis that could be produced in guinea pigs. He also proposed the causal role of allergy in asthma, seasonal allergic rhinitis, and certain skin diseases.
  • Early 1900s Physicians interested in allergies, including William Philipps Dunbar, Leonard Noon, and John Freeman all experimented with immunizations against seasonal allergic rhinitis, forming the basis for immunotherapy. During this time, Sir Henry Hallett Dale and Sir Patrick Playfair Laidlaw described histamine as a potent vasoactive substance. Dale learned that injection of histamine produced an anaphylactic-like state and therefore suggested that histamine had something to do with anaphylaxis. He became the first to describe the fixation of anaphylactic antibody to cells before its reaction with the antigen.
  • 1910-1930 Interest in allergies increased dramatically and clinics for the study of allergic disease sprang up across the United States. Attempts at immunotherapy continued, but were often conducted without adequate controls and poorly recorded. The genetic component of allergies was also observed during this time, with Robert Anderson Cooke reporting that forty-eight percent of patients with allergies had family histories of the condition.
  • 1921 Otto Carl W. Prausnitz identified what was later called “reagin,” and what is now known to be immunoglobulin E (IgE) antibody. He found that it was present in higher quantities in allergic individuals.
  • 1927 Sir Thomas Lewis described the “triple response” of skin to mechanical stimulation, which led to the histamine theory. This theory is the idea that a diffusible “H-substance” with chemical properties like those of histamine, was released as part of a local, specific reaction to an allergen.
  • 1935 Robert Anderson Cooke and Mary Hewett Loveless described elevated blocking antibody levels after injections of allergenic extracts. This started a new era of investigations into the mechanisms of the allergic response.
  • 1950s Immunoglobulin A (IgA) was discovered by Thomas B. Tomasi, Jr. Later, Kimishige and Teruko Ishizaka, building on Tomasi’s work, proposed that IgA could be responsible for human atopy and allergies. However, subsequent work by Loveless and others demonstrated that this wasn’t the case.
  • 1967 The Ishizakas identified the skin-sensitizing, reaginic antibody as IgE. They discovered a new immunoglobulin class, gamma E globulin. Two Swedish researchers, Hans Bennich and S.G.O. Johansson, had been working on the same issues, and upon meeting with the Ishizakas, realized they were studying the same class of immunoglobulin. They agreed to call it IgE, which was recognized as having all the biological features of reaginic antibody. These studies formed the basis of modern immunological research on allergic disease.

• 1980s Bengt I. Samuelsson described the bronchoconstrictor, chemotactic, and pro-inflammatory properties of leukotrienes, contributing significantly to the understanding of their biological role in asthma, allergy, and inflammation.

By going through the history of allergies from earliest recorded history of the affliction through to the advances that have formed the basis for our current research, we hope to have given you some insight not only on the long, long co-existence of humans with allergies, but on the advances that have been made and will continue to be made in the field of allergic disease.