1910-1950: Antihistamines to treat allergies

While some scientists and physicians studied the effects of decensitization for the treatment of hay fever (er, allergy) sufferers, others were working on other angles.  This was a good thing, because one of the best selling medicines of all time was the result. 

In 1910 British scientists discovered a chemical called histamine that was released during an allergic reaction, and they determined it was this substance that was responsible for causing tissues to become inflamed.  A year later Henry Dale proved that injecting histamine into guinea pigs and dogs would instigate the allergic response.

This discovery gave scientists a lot of hope.  Originally they beleived histamine was the only cause of allergies and that finding a treatment for histamine would mean allergies would be eliminated.  Yet later scientists learned this was not true, that allergies were a series of complex reactions.

In 2007 Gregg A. Minton explains how "in 1921 Carl Pransnitz attempted to further understand allergies by injecting into his abdomen the serum from his colleague Heinz Kustner, who had a severe allergy to fish.  Prausnitz had no such allergy, but when he sat down to a fish dinner, he found that a case of the hives appeared on his body at the injection site. The experiment demonstrated that a specific immune body -- later known as an antibody -- was present in the serum of allergic patients.  The substance could be passively transferred to nonallergic individuals, and it played a crucial role in the allergic reaction." (1, page 215)

This experiment lead researchers to think that if they could figure out what this "antibody" was they could unlock the mystery of allergies and eliminate this annoying malady from existence. (1, page 215) So the hunt was on. 

In the meantime, Daniel Bovet introduced a medicine that blocked the effects of histamine in 1937, and he called this new medicine an antihistamine.  It was the first truly effective medicine to treat the symptoms of allergies.  By blocking the effects of histamine it therefore prevented an allergen from causing a stuffy and runny nose, itchy eyes, nose and throat, and sneezing.

The next discovery was Benadryl.  Minton explains it was discovered by 21 year old professor at Cincinnati University named George Rieveschi.  He was trying to create an antispasmotic drug when he inadvertently discovered the "new compound in his laboratory." (1, page 216)

In 1946 the first two antihistamines hit the market:  Benadryl and Pryibenzamine. Minton describes how "antihistamines became, next to antibiotics and barbituates, the third most commonly prescribed class of drugs in America." (1, page 213)

Minton explains that other antihistamines hit the market in 1947, but Benadryl and Prybenzamine made up the bulk of the sales.  In 1947 Hydrillin hit the market, which was a product that had both an antihistamine and a bronchodilator called theophylline. This relieved allergy symptoms and made breathing easier, an ideal remedy for people suffering from allergic asthma (which, as it turns out, includes about 75 percent of all asthmatics)

Theophylline is a medicine that was first introduced to the world in 1930 as another antispasmotic medicine for asthma.  It was a medicine that relaxed the smooth muscles that lined the air passages of the lungs and made breathing easier.  This new medicine provided another over the counter option for allergy and asthma sufferers. (I wrote about theophylline here.)

In 1949 Neohetramine was the first antihistamine approved by the Food and Drug Administration (FDA) as an over the counter medicine.  Other antihistamines soon followed.  Minton notes that "by 1950, more than 21 antihistamine compounds packaged under one hundred different trade names in tablets, nasal sprays, eye drops, and creams on the market in the United States." (1, page 216-217)

References:

1. Mittman, Gregg, "Breathing Space," 2007, New Haven and London, Yale University Press

1862: Phoebus studies 'summer catarrh'

Christian Freidrich Schonbein (1799-1868)
While not the first to mention ozone,
he was the first to produce it in a lab.
He wrote about how to make it in 1832.
He also noted that air containing ozone
caused certain catarrhal conditions,
including asthma and hay fever.
Phoebus noted the link in 1862,
and usually gets credit for it
(5, page 80) (6, page 311)

Since Dr. John Bostock defined hay-fever for the medical community in 1819 and 1828, there was little mention of the ailment until Dr. Philip Phoebus published a book titled "On the Typical Catarrh of Early Summer, or the so called Hay-fever or Hay-asthma" in 1862.  (1)

Dr. Phoebus was professor of medicine at the University Giessen in Germany, and he was apparently one of the first physicians to study hay fever who did not have the condition.  He is said to have gained interest in it by the single case that he treated.  (4, page 17)

In 1869 he issued circulars and advertisements inviting medical men all over Europe and the United States to respond to seven questions phrased to gain particular information regarding their patients diagnosed with hay fever. The questions were well worded to gain particular information, and were related to the following: (2, page 14-15) (3, page 2) (4, page 17)

1. Where they lived (city, country, lowlands, mountains, etc.?)
2. What they did in their every day lives (lawyer, doctor, industrial worker, farmer, etc.?
3. Their sex (male or female?)
4. Social position (rich, middle class, poor?)
5. Inheritance (was their disease hereditary? Do they have parents, grandparents, or siblings with the condition?)
6. Constitutional peculiarities (does it affect their health and well being?)
7. When do attacks of hay fever occur? (autumn, winter, spring, summer?) (2, page 14)

He received many replies, and used the information he received to put together a complete theory about this disease.  He then published the results of his research three years later, in 1862, in a thorough treaties. (2, page 14-15)

He learned that hay fever was most common in England than any other nation of Europe.  He learned people were predisposed to it, although he didn't understand why.  (2, page 15)

He believed the exciting cause was the first heat of summer, and that the longer days of summer exposed those predisposed to it to more light, and probably more ozone too.  In this way he was among the first to suspect a link between air pollution (ozone) and hay fever or hay asthma. (2, page 15)

He also believed that odors, dust, the blossom of rye, and hay were also exciting causes. (2, page 15)

In reviewing the ideas regarding of Dr. Phoebus on hay fever, Dr. William Abott Smith said Phoebus described six groups of symptoms, of which may vary from one case to another. (1, page 16)

1.  Nostrils.  Severe catarrh (common cold) leads to sneezing, and this may irritate the bronchi, causing spasm.  (1, page 17)

2.  Eyes.  Catarrh and increased secretions. The eye feels full, itchy and irritating.  The eye looks red and swollen.  Eyesight is weakened, and there is an intolerance to light. Both eyes are usually affected simultaneously. (1, pages 18-19)

3.  Throat. Pharynx is red, and swollen; there is intense itching of the back of the mouth behind the tongue.  This causes an unpleasant sensation that is aggravated by the patients efforts to relieve the itching. Sometimes there is difficulty swallowing. (1, pages 19-20)

4.  Head.  A headache might occur, that might be caused or worsened by sneezing.  The patient might also complain of a feeling of itching over the forehead, nose, chin and ears. (1, pages 20-21)

5.  Airway.  The mucus  membrane of larynx all the way to the bronchi may become irritated, causing asthma or dyspnea.  This may result in a cough, increased sputum production, irritation of the throat, a heavy feeling over the chest, and a muffled and coarse voice.  If the bronchi become affected, this may result in wheezing that results from bronchial catarrh or asthma or, more specifically, hay asthma or periodic asthma.  Dyspnea generally occurs in the evening and continues through the night. Hay fever that affects the lungs in this way tends to be more severe, with the patient waking up gasping and struggling to breathe. (1, pages 21-22)

6.  Nervous disturbance.  This is coupled with catarrhal fever that results in shivering and cold perspirations with sneezing and coughing. When this happens the patient becomes restless, weary, and unable to perform normal activities. The patient becomes irritable, with something as simple as a cool breeze being disturbing to the patient.  These patients generally develop a nervous and anxious disposition during the paroxysm. (1, page 22)

All in all, Dr. Phoebus went into more detail on hay fever, what causes it, and the symptoms that resulted, than any of his predecessors. Yet, and he knowingly admitted, he left many questions still unanswered for future investigators to answer. (2, page 15)
---------

Dr. Blackley took the observations of Phoebus and Schonbein regarding their suspected link between hay fever and ozone, and set out to perform experiments with the substance.  He spent six hours in his office inhaling the substance and observed no effect. (11, page 35) (8, page 8, pages 79-91)

However, while he proved ozone had no effect on hay fever, he became the first to suggest that dust might cause hay-fever symptoms.
-----------

References:

1. Smith, William Abbotts, "On Hay-Fever, Hay-Asthma, or Summer Catarrh," 1867, London, Henry Renshaw, pages 17-24. 
2. Beard, George Miller, "Hay Fever; Or, Summer Catarrh: Its Nature and Treatment," 1876, New York, Harper & Brothers, Publishers
3. Wyman, Morril, "Autumnal Catarrh (Hay Fever)," 1872, New York, Published by Hurd and Houghton, The Riverside Press
4. Mackenzie, Morell, "Hay fever and paroxysmal sneezing," 5th ed., 1889, London, J&A Churchill
5. Blackely, Charles Harrison, "Hay-fever: its causes, treatment, and effective prevention," 1873, 1880 2nd edition, London, Bailliere
6. Dickenson, Samuel Henry, "Elements of Medicine: a compendious view of pathology and therapeutics, or the history and treatment of diseases," 1855, Philadelphia,  Blanchard and Lea

RT Cave on Twitter

1901-1920: Hay fever becomes allergy

Paul Portier

The term hay fever was used for the first time in medical nomenclature in 1812 by Dr. John Bostock to describe seasonal allergy symptoms associated with the hay season. The term had been used by lay people much longer than that. So, even while many physicians doubted it was an appropriate term, it stuck in medical nomenclature like gum on a little boy's shoe.

However, a series of discoveries shortly after the turn of the 20th century would introduce the world to a series of new terms, such as anaphylaxis, atopy, and allergy.

In 1901, the Prince of Morocco summoned two scientists, Paul Portier and Charles Richet, to study a sea anemones called the Portuguese man-of-war. Their job was to learn how to protect swimmers from its sting, which caused painful blisters. (1, page 608)

Initially, the two believed the painful blisters were caused by toxins from the animal's tentacles once they were entered into the skin of humans.  Back then vaccination was becoming a household name, and so the two set out to create an antitoxin vaccine.  (1, page 608)

Richet started the experiment by extracting toxins from sea anemones, and gave them in small amounts to test dogs.  After the initial injection they figured the dogs would develop antibodies that would protect them from a second exposure of the toxin.  In this way they would develop a natural protection against it, or prophylaxis.

Charles Richot

However, when they extracted the toxin of sea anemones and inserted it into test animals (dogs in this case), the reaction they got was the opposite of what they expected.  The first two doses did no harm to the animals, but subsequent doses caused many of the dogs to go into a state of shock, and most did not recover.  Richet and Portier determined the animals died due to the effects of the toxins.

Instead of prophylaxis The animals developed aniphylaxis, a new term devised by the two men.

It's time for some definitions:

• Greek pro means toward or before
• Greek phylaxis means protection
• Greek ani means opposite or away
• Prophylaxis means to add protection
• Aniphylaxis means to cause harm

So, instead of protecting the animals from developing symptoms, they caused the symptoms.  The scientists learned that a "foreign protein" was transferred from the sea anemones to the dogs making them hypersensitive to that protein. (2, page 11)

Other scientists performed similar experiments and came to similar results.

Clemons von Pirquet

In 1906, an Austrian pediatrician named Clemons Von Pirquet observed many of his patients were hypersensitive to substances that didn't bother other people.  These normally innocuous (harmless) substances were pollen, dust mites and some foods.

The purpose of the immune system is to attack foreign particles that want to harm the human body.  Yet sometimes the immune system attacks allergens that are not meant to cause harm.  Von Pirquet and Schlick observed this, and they coined the term allergy to describe when the immune system causes harm.  (5, page 53)(3)

Once again a definition is in order:

• Greek allos means other
• Greek ergon means action or enery
• Allergy means the immune system causes the opposite effect as its intention (causes harms)
• Allergen means a substance or protein that may incite the allergic response hen a hypersensitivity is present
• Hypersensitivity means over-reaction; a hyper-reaction of the immune system; as in when exposed to allergens (Dated to 1870s)(Dictionary.com)

Von Pirquet actually believed that asthma was an allergic condition, and curing this disease was only a matter of finding the right foreign proteins to inject. History would prove him right in juxtaposing asthma and allergies, yet wrong on the front of this leading to a cure.

Also in 1906, German physician Alfred Wolff-Eisner surmised that pollen is similar to the poisons of the Portuguese man-of-war in that it could trigger the immune response in some some people.  By inserting drops of pollen into the eyes of volunteers, he was able to produce the same response suffered "during the hay fever season: red, swollen, and itchy eyes." He published his findings in 1906.  (5, page 54)

Thanks to Wolffe-Eisner's discovery linking hay fever with the immune system, hay fever was no longer believed to be a nervous disease.  It as no a disease caused by a hypersensitive immune system. This was an essential transformation because it would effect the future course of treatment for the disease.  Instead of seeking to alleviate a nervous disorder, the goal of treatment as not to fix a broken immune system.  (5, page 54)

In 1910 Samuel Melzer observed the "similarity" between anaphylaxis and asthma "in which a person became sensitized to a definite substance, and an attack occurred every time the substance entered the circulation (of that patient).  Minute quantities of the substance, if inhaled, would bring on an asthma attack." (2)

We now know that about 75 percent of asthmatics have allergies.  Yet we also know that many people have allergies and not asthma.  We also know that both conditions have been linked to the immune system and can be developed at any age.  Yet in 1906 scientists were at the dawn of such allergy wisdom.

Pirquot believed it was the body's response, not the foreign particles, that resulted in the allergic reaction. He listed as things that might cause this "hypersensitivity" as bee stings, mosquito bites, hay fever caused by pollen, and substances in certain foods such as crabs.

Soon thereafter Arthur C. Coca, founder of the Journal of Immunology, and Robert Anderson Cook, were attempting to understand studies regarding allergic conditions, used the term Atopy which literally means "strange disease."  They thought atopy should be used to describe hereditary hypersensitivities such as asthma, hay fever and eczema, and hypersensitivities that could afflict anyone should be referred to as anaphylaxis.

By 1919 two allergists, Cooke and Albert Vander veer, published the results of a study of 500 patients with asthma, hay fever, and other allergic diseases that confirmed that age old theory that these conditions were inherited and perhaps linked to other conditions.

Initially all prophylactic and anaphylactic reactions were referred to as allergies, as this as the recommendation of Van Pirquot.  He believed the two reactions should have a common name.  (3)

Yet ultimately it was learned that there were three conditions associated with hypersensitivities that didn't fit into this classification:  asthma, hay fever and eczema.  In asthma the hypersensitive response lead to constricted air passages, in hay fever it lead to a runny and stuffy nose, and in eczema it lead to red and itchy skin.

These three conditions -- asthma, hay fever and eczema -- are now often referred to as the atopic triad because in many individuals they come as a package.  One major difference between the atopic triad and anaphylactic reactions is that anaphylaxis can be induced in almost anyone, while the others occur in only a small percent (about 10 percent) of individuals and are quite often hereditary.  (4, page 608)

In subsequent years allergy was used to denote an immunal hypersensitivity or hyperresponsiveness to a foreign substance and atopy was used to denote the inherited conditions of asthma, hay fever and eczema.  Although, quite often the terms allergy, atopy and anyphylaxis are used interchangeably.

References:

1. Klein, Jan and Vaclav Horejsi, "Immunology," 1997, page 608
2. Brenner, Barry E, "Emergency Asthma," (ed. Barry E. Brenner), 1998, New York
3. Ehrlich, Paul M., Elizabeth Shimer Bowers, "Living with Allergies," 2008
4. Klein, Jan, Vaclav Horejsi, "Immunology," 1997, page 608
5. Mittman, Gregg, "Breathing Space," 2007, New Haven, London, Yale University Press

625-690: What did the ancients think of colds and allergies?

Viral and bacterial infections, common colds, allergies, hay fever, rhinitis and other such affections of the upper respiratory tract were generally all considered one and the same thing for most of history.

They were generally referred to as coryza, catarrh, and cough.  They were basically symptoms, and therefore the disease.  Coryza being inflammation of the nasal passages, catarrh being increased mucus and discharge in the nose and throat, and cough being a cough.  (1, page 469)

Paulis Aegineta, our Arabic medical historian from the 7th century, said "All these complains have this in common, that they are occasioned by the defluxion of a redundant humour  from the head to the parts below.   (1, page 469)

This basically meant that there was too much phlegm in the brain, and when this occurs it spreads to the nasal passages, mouth, throat, and lungs.  Therefore, the same cause also resulted in diseases of the throat and lungs, including croup and asthma.

Aegineta generally worded it this way:

When, therefore, it seats in the nostrils, the disease is called coryza; when in the pharynx and roof of the mouth, simply catarrh; but when it attacks the larynx and arteria trachea, so as to occasion a roughness of the membrane which lines them, the voice becomes hoarse, and the disease is called branchus, or morbus arteriacus: these terms being applicable not only to the inflammatory roughness occasioned by a defluxion from the head, but also to that arising from vociferation and inhaling cold air. (1, page 469)

It makes sense that they believed it was caused by inhaling cold air, considering people are more likely to catch a virus or bacteria when huddled close together in a warm room due to cold weather outdoors.  Yet they would have associated it with the cold air.

Cough pneumonia and influenza were also likely to be caused by the same thing. Aegineta said:

When the complaint is protracted, and the defluxion is carried down to the chest and lungs, it gives rise to bad coughs. And a cough often arises from an intemperament; sometimes a hot one, as in fevers, and sometimes a cold, as in northerly states of the weather, which is rather a dry one. Cough is also sometimes symptomatic of some other disease, such as pleurisy, hepatitis, phthisis, or peripneumonia. (1, pages 469-470)

Another disease would have been chronic bronchitis, which was not officially a disease until many centuries later.  Paulus might have been referring to this when he wrote:

Wherefore Galen relates that, in certain chronic cases of cough, chalazia (hail-stones) have been brought up from the chest. But Alexander relates that a certain heavy stone, like that which forms in the urinary organs, was brought up in a chronic cough, upon which the cough ceased. (1, page 470)

 Paulus lists the following as remedies for coryza and catarrh: (1, pages 470-471)

• Baths, and have a large quantity of hot water poured upon the head
• Foods such as spoon-meats and eggs in a state to be supped, starch, sweet cake, sesame, rice, almonds, the fruit of the cones of pine, and all confections from milk. 
• The wines which are drunk should be sweet and not old.
• A restricted diet is to be observed, and the head anointed with some heating and attenuating ointment, such as that of nard or rue.
• The ointment of iris is not only to be rubbed in, but is also to be injected into the nostrils
• Internally, they are to be rubbed with frankincense and myrrh, with oil; and this more especially when the coryza arises from cold.
• Odoriferous substances with burnt linen, or by gith and cumin burnt and bound up in a linen rag.
• Let them also smell to the cyphi seleniacum, and let it be rubbed into the forehead; and to it let there be added one of the antiphlogistic plasters, such as the Icesian, the Oxera, the Barbarum, and the Athena.
• For catarrh from cold it will be expedient to drink of cyphi, and to rub into the chest the juice of balsam by means of unwashed wool
• Apply calefacients to it (the chest), along with storax, the ointment of iris, or that of dill. 
• Let them also use hot and concocting food. But when the matter is already concocted, a masticatory will answer well with them, and detergent ointments (smegmata) to the head, such as the soap of Constantine, and the like (1, pages 470-471)

For affections of throat and trachea and coughs, the remedies are essentially the same, so I won't go into them.  Chances are none of these remedies did much good anyway, other than to have a placebo effect.

He does, however, offer some recipes for pills that might be useful for catarrh and cough.  He said:

Of storax, of myrrh, of opium, of galbanum, equal parts; mix with must, or pound by themselves in a mortar, and make into pills the size of a tare. Give three, four, or five at bedtime, and swallow with some must. These things are for an acrid and thin rheum.—Another: Of the seed of henbane... of pine-nuts... of saffron.  Mix with rob or with must, and use. An electuary. Of honey  of butter.... Boil together and give; and let the decoction of hyssop, of figs, of pinenuts, and of iris, be swallowed. Pills for more inveterate coughs. Of storax... of myrrh... of turpentine, of galbanum, of opopanax, and of iris, of each..., of white pepper, of nitre, of henbane-seeds, of the juice of poppy, of each... Beat in a mortar without any liquid, form into pills, and use as formerly directed. (1, page 472)

Francis Adams said that most of the other ancient physicians, with the exception of Aretaeus, agreed with Paulus Aegineta regarding his description and treatment of coryza, catarrh, cough and common throat ailments. The same is true of Arabian physicians.  So we have no reason to delve into their thoughts on the subject. However, if you want to learn about them, you can click on the link provided below. (1, page 472)

However, it must be understood that most physicians, no matter what era they are from, have form their own opinions about diseases and their remedies, and so how you were treated would depend on who your physician was.

Don't scratch your head trying to figure out what all these remedies are or what they amount to.  I just wanted to show you what some of the remedies would be if you suffered from the common cold or allergies in the ancient world.  

Chances are, you'd be better off toughing it out, which is probably what most people did.  

References:

1. Aegineta, Paulus, "The Seven Books of Paulus Aegineta," translated by Francis Adams, volume I, 1844, The Snydenham Society, pages 469-475 

RT Cave Facebook Page
RT Cave on Twitter