1873: The Blackley Experiments, part IV

The results of a scratch test performed on a boy.

During the summer of 1865,  Charles Blackley performed perhaps his most famous experiment. He obtained pollen from Lolium Italicum and applied it to one forearm of a friend. He then scratched the skin over the pollen to introduce it to the skin. He did the same to his friends other forearm, although without applying pollen.

Soon thereafter he observed that the skin around the scratch where the pollen had been introduced to the skin tissue "raised a wheel such as is seen in uticaria or in stinging with nettles. In a few minutes, after the pollen had been applied the abraded spot began to itch intensely; the parts immediately around the abrasion began to swell, but this was not apparently due to any action on the cutis vera (skin)."(1, page 105) (2, page 818)

He observed that the rash was contained to the area around the scratch. He wrote:

The tumour increased in size until it measured two and a half inches in length, by one inch and a half in breadth, and was raised above the ordinary level of the surface nearly three quarters of an inch. No pain was felt in the limb, nor was there any heat or redness present at any time, beyond the very slight amount to which the abrading of the cuticle gave rise. The swelling attained its maximum in six hours, and then remained stationary for other eight hours; after this it gradually subsided, and in forty-eight hours it had entirely disappeared. The arm to which no pollen had been applied did not exhibit any sign of swelling or irritation.

Blackley performed this experiment to show that a rash was a specific result of pollen. This test has been modified some over the years, but it is still used to this day to test people for allergies. It is called the scratch test.

If a doctor suspects a patient has allergies, he can place a variety of allergens on the surface of the patient's skin, either on the forearm or back, and scratch the surface of the skin over each specific allergen. if a hive forms the patient is allergic to that allergen.  If no hive forms, the patient is not allergic to that allergen. The size of the hive also helps to reveal the severity of the allergy. For example, a large hive would be the result of a severe allergy to that substance.

He would continue this practice until he retired in 1894.  He passed away in 1900 at the age of 80.

References:

1. Blackley, Charles Harrison, "Experimental Researches on the Causes and Nature," 1880, 2nd edition, London, Bailliere, Tindall, and Cox
2. O'Sullivan, Dr. Stephen, "Charles Blackley and Allergy Research," New Scientist, June 28, 1973, Volume 58, No. 852, pages 818-819

1873: The Blackley experiments, part III

Plate showing an apparatus used by Blackley to collect pollen.
This design was recommended by Dr. Philipp Phoebus.
Any solid particles in the air collected on a glass plate (d),
that was exposed to a specific atmosphere for 24 hours.
The glass plate was then examined using a microscope.
The number of pollen counted.
(1, page 122)

Charles Blackley wasn't your typical hay fever patient. After suffering from its annoyingly frustrating symptoms year after year, and realizing his experiences with the disease did not match what was offered in medical literature, he began, in 1859, a series of experiments to prove the actual cause and nature of this disease. His ultimate goal was to find a remedy that actually worked.  Or, better yet, a cure.

This was probably an exciting time for Blackley.  He knew there was not much written about hay fever, and what was written was mostly speculation, so there was still a lot to learn about this newly defined disease.

By reading newspaper accounts, or perhaps by listening to his professors, he must have been well aware of all the recent investigations on microscopic substances. He most certainly would have known of recent studies on the reproduction of plants, and that it was determined plants reproduce sexually.

He must have learned about pollen, and how some plants were pollinated by bees and others by wind.  He must have been well aware that pollen was in the air around him, and that a few physicians had speculated this pollen might be a contributing cause of hay fever symptoms, although it was never proven.

The idea that diseases could be caused by microscopic substances was proven by Louis Pasteur.  Perhaps Blackley was thinking of this as he went to his bedroom one spring night.  Perhaps he was symptom free when he opened the window to enjoy the refreshing breeze, but was sniffling and sneezing upon waking up. Perhaps it was this that caused him to have an aha moment.

Blackley and his friends spent many hours in enclosed rooms inhaling, sniffing, and rubbing onto their respiratory membranes and eyes and lips all the substances suspected of causing the symptoms.  When none of them caused the symptoms of hay fever, they must have gotten excited that they were on to something truly historic here.

This excitement must have become exuberant when the first experiments on pollen came back positive for hay fever symptoms.  The only frustration was when a test came back positive they had to wait for the symptoms to abate before performing the next test on himself.

However, even when he was having symptoms, he was able to study the types and quantities of pollens in the atmosphere.  To do this, he constructed an apparatus (see figure) that allowed him to collect and count pollen for 24 hour periods in various locations "to imitate some of the conditions... to which a patient may be exposed in his daily routine." (1, page 122)

As he suspected to be the case, his own hay fever symptoms appeared to be worse on the days when the quantity of pollen in the air he was studying was highest. (1, 124-125)

By using his apparatus to count pollen on both hot days and cool days he was able to conclude that the quantity of pollen was determined by the temperature of the air.

Because he failed to measure the moisture of the air, he was unable to use his experiments with the apparatus to determine the effects of humidity on the release of pollen.  So he opted to perform a separate experiment where he allowed several ears of rye to grow in a dry controlled environment, and several more to grow in a humid controlled environment.  (1, pages 126-7)

The ears exposed to dry air threw off their pollen within a few hours, and the ears exposed to high humidity threw off no pollen.  This test proved the release of pollen was greater on dry days than humid days.  (1, pages 126-7)

By using his apparatus to collect pollen on rainy days, he quickly realized that rain was not conducive to the release of pollen.  This explained why some hay fever patients observed a reprieve from hay fever when the rain was falling.  (1, page 121)

However, he concluded: (1, page 86-87)

A high temperature is in itself favorable to the generation of pollen, but a high temperature with severe drought will, in the case of the grasses, check their growth, and thus prevent the formation of pollen. In proportion as temperature and moisture are suitably combined, so will be the production of pollen, but where these happen to be unusually favorable, we may have the grass arriving at maturity rapidly, and as a consequence this may be quickly cut and converted into hay and housed. Under such circumstances, hay-fever patients may have a short season of attack, but the symptoms may be very severe whilst they last. (1, pages 86-87)

In the same manner, he proved that grass did not grow well at lower temperatures, and grass that did grow had less vigor.  Likewise, plants that flowered prematurely, such as in March, did not have the same power as when the plant flowered in the middle of summer. (2, page 87)

Because pollen counts may peek during the dog days of summer, Blackley said he could understand how such an intelligent physician as John Bostock might confuse heat as the cause of the malady. Yet Backley now understood that heat was a contributing cause more so than the exciting cause.

He learned that the amount of wind affected pollen counts too. He said:

A quiet state of the atmosphere in the height of the hay season generally gave a large amount, but a strong wind lessened the quantity. In the latter case, however, if the wind was not very strong, I found the ophthalmic (tissue around the eyes) suffering to be more severe than in a quieter state of the atmosphere. (1, page 121)

Various physicians recommended a visit to the city in order to obtain a reprieve from hay fever symptoms. While previous authors did not understand why this was so, Dr. Blackley proved by his experiments that it was because there was less pollen in the middle of a city. (1, page 121)

And, most notably, many physicians recommended hay fever vacations to the seashore at high altitudes, such as in the mountains.  Dr. Morrill Wyman recommended hay fever vacations, particularly to the White Mountains.

References:

1. Blackley, Charles Harrison, "Experimental Researches on the Causes and Nature," 1873, London, Bailliere, Tindall, and Cox

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1873: The Blackley experiments, part II

Of all the things theorized to cause hay fever, Dr. Charles Harrison Blackley put them all to the test on himself.  The following are the common agents he tested:

1.  Benzoic acid:  It's a compound used as a food preservative.  In three different experiments, he inhaled vapors and fumes of the substance, and applied a solution of it to the mucous membranes inside his nose.  His conclusion was that the substance did not cause hay fever symptoms. (2, pages 51-53) (5, page 71-73)

2.  Coumarin:  A chemical compound found naturally in some plants, and can be used as a food additive or in some perfumes.  He placed ten drops of the substance upon a plate, thus allowing it to evaporate into the air of the room.  He and a couple friends entered the room, spending a couple hours at a time on more than one occasion.  The men walked around the room as to inhale the air as if they were walking in the open air. He even performed this experiment in different years and during different seasons of the year.  The experiments did not produce hay fever symptoms. (2, pages 53-55) (5, pages 73-75)

3.  Odours: He inhaled the odours of various plants, flowers, fungi and other substances.   Some produced hay symptoms and some others didn't.  The substance that came closest to producing hay fever symptoms was Penicillium. His recommendation was for further testing in this area. (2, pages 55-59) (5, pages 76-79)

4.  Ozone: It was discovered in 1785 by Dutch physicist Martinus Van Marum (1750-1837), and is a naturally occurring substance created by the sun.  Christian Friedrich Schonbein described in 1832 how it can be produced by man. Dr. Schonbein said he observed catarrhal affections such as asthma and hay fever among those who, during experiments he performed, inhaled air highly charged with it.

During the 1850s various other physicians made similar observations, and so did Dr. Phillip Phoebus in 1862.  Blackley set out to prove if this was true.  In some experiments he spent several hours, at various seasons of the year, in locations with high levels of measurable ozone in the atmosphere, and he observed no hay fever symptoms.  He also artificially created an atmosphere high in ozone in a room, and he spend six hours in it while experiencing no ill effects.

He also observed that ozone was always present, even in the atmosphere on the seashore and out at sea, where many hay fever sufferers have reported relief of symptoms. He therefore concluded that if ozone caused hay fever, symptoms would be observed in these locations.

In this way he was able to disprove the theory that ozone caused hay fever symptoms. (2, pages 59-69) (2, page 8, pages 79-91)

5.  Dust: Blackley said many authors referred to dust as "common dust," and he said there is no such thing, as all dust contains different ingredients depending on the geological character of the district and its botanical productions. He said various germs may also appear in the dust depending on temperature and moisture of the air.

He said dust produces hay fever symptoms, but only during the hay or flowering season.  He did observe that symptoms occurred when a horse and buggy stirred up dust, but he attributed this pollen carried carried by the horse and buggy and not the dust.

In other words, he attributed symptoms caused by dust not so much on the dust, but on pollen mixed with the dust. He said he would further prove this by performing experiments with pollen.  (2, pages 69-72) (5, pages 90-93)

6.  Pollen: He performed five different types of experiments with various types of fresh and dry grass and flowering pollens: he applied them to the mucous membrane inside a patient's nose, he had the patient inhale them to bring them into contact with the throat and lungs, he applied them to eyelids and lips, and he rubbed them on limbs.  (2, page 76)

Upon completion of his experiment on pollen, he said:

Almost every experiment (with pollen) is by a greater or smaller amount of definite and unmistakable effect which seems to point to pollen as the most powerful if not the only cause of the malady. (2, page 74)

In this way, he proved that, without a doubt, pollen was the main cause of hay fever, both in its catarrhal and asthmatic forms.  He also determined that even a small amount of pollen may cause these symptoms, although the severity depended on the type and the quantity of pollen. (2, page ?, 99)

7.  Animals:  Various physicians had noted that some animals, such as cats, rabbits and guinae pigs, brought about hay fever symptoms.  Blackley suspected that this was due to pollen being carried withing the fur of these animals. (2, pages 101-102)

8.  Light:  Regarding this, he said:

We have abundant evidence to show the important influence it has in aiding those changes that make up the sum total of life in the animal and vegetable kingdom, but we have no evidence to show that it has the power to produce symptoms which have even a remote resemblance to those of hay fever, and, so, as far as I am aware, no author has yet made experiments which prove that light can produce the fully developed disease." (2, page 102)

He said that until evidence shows otherwise, he cannot accept that light is the cause of hay fever. (2, page 102-103)

9.  Heat: Many credible physicians, including Dr. Bostock, postulated this to be the cause.  However, if this were true, hay fever sufferers would not get a reprieve while visiting the city or the sea side, as the weather would be the same at these locations as anywhere else.  He said the disease would equally appear in southern states as northern states, and in fact Dr. Morrill Wyman proved there are fewer cases of hay fever in the south.

Blackley essentially said John Bostock's experiments that showed hay fever was caused by heat were flawed.  Blackley said:

I have... shown that in a cool summer very little pollen is formed by grass, and I shall be able to show... that a rise in the temperature, during the hay season, will sometimes cause large quantities of pollen to be formed and thrown off... certain it is that heat and moisture favor the growth and evolution of pollen and that cold and dryness will almost completely put a stop to these processes. (2, page 104-105)

Lacking this knowledge, it must have been easy for wise physicians like John Bostock to assume that heat was the cause of the symptoms, instead of just a contributing factor.

References:

1. "Charles Harrison Blackley, 1820-1900," The University of Manchester: The John Ryland University Library: Manchester Medical Collection, http://archives.li.man.ac.uk/ead/search?operation=full&rsid=dc.title%20any%2Frelevant%2Fproxinfo%20%22William%20Charles%20Henry%22&firstrec=1621&numreq=20&highlight=1&hitposition=1638, accessed 9/13/14
2. Blackley, Charles Harrison, "Experimental Researches on the Causes and Nature," 1873, London, Bailliere, Tindall, and Cox
3. Waite, K.J., "Blackley and the development of hay fever as a disease of civilization in the nineteenth century," Medical History, April, 1995, 39 (2), pages 186-196, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1036974/?page=5, accessed 9/14/14
4. Smith, William Abbotts, "On Hay-Fever, Hay-Asthma, or Summer Catarrh," 1867, London, Henry Renshaw, pages 17-24.
5. Blackley, Charles Harrison, "Hay Fever: It's causes, treatment and effective prevention," 2nd edition, 1880, London, Bailliere, Tindall, & Cox

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1873: The Blackley experiments, part 1

Charles Harrison Blackley (1820-1900)

Dr. John Bostock defined hay-fever in 1819, and by 1840 it quickly gained ground as a common diagnosis. This was true despite physicians not understanding the true cause and nature of the disease. Yet this all changed in 1873 when Charles Harrison Blackley published his book "Experimental Researches into the Cause and Nature of Catarrhus Aestivus."

He was born in 1820, and when he was of age he became an apprentice to Bradshaw as an engraver and printer.  (3, page 190)

In 1848, at the age 28, he became ill and became a patient of Dr. David, who practiced in homeopathic medicine, or medicine that was generally shunned by the medical profession.  He was diagnosed with a newly defined disease called hay fever.  This seemed to have peeked his interest in both homeopathic medicine and hay fever. (3, page 190) (2, page 8)

He continued to work as a printer and engraver, studying chemistry, botany, electricity, and Greek on the side.  In 1855, at the age of 35, he left this career to attend Manchester School of Medicine full time.  He qualified as a doctor in 1838, and started a practice in Manchester, England, as both as a surgeon and physician, specializing in homeopathic medicine. (1) (3, page 190)

He returned to school in 1874, this time at Brussels, where he earned his doctorate (M.D.). He did not hide the fact he practiced in homeopathic medicine, in fact he was honored and even wrote papers on the subject. However, once he obtained his doctorate (M.D.) in 1874, he was more generally accepted by the medical community. (3, page 190) (1)

Through it all, and since his diagnosis with hay fever, and his constant reminder of it each fall, he constantly and "carefully read over most of the scanty bits of literature of the disease then existing," he said.   (2, page 8) (3, page 190)

He learned there were a lot of theories as to what caused hay fever, including heat from the sun on hot days, benzoic acid used as food preservatives, strong odors (such as from plants), ozone, dust, light, animals and pollen (from grass or flowering plants).  Yet he was constantly frustrated by the lack of evidence that any of these caused hay fever. (2, pages 3,7)

He was amazed at all the theorizing regarding the cause and nature of this disease. He said: "It is, however, much easier to theorise than to try experiments, and especially when these would have to be tried on the theoriser's own person. (2, page 73)

He said such theorizing resulted in "no advance towards obtaining a remedy on which we can depend as an effectual means of a cure," he said.(2, page 3, 7)

The most common theory at the time was that hay fever was caused by heat, such as heat from a hot summer's day.  However, one day he was in a hot kitchen and he did not have hay fever symptoms.  He wondered why this would not induce the symptoms, but a hot summer day would.  It made no sense.

He said:

"I was inclined to regard heat as the principle exciting cause, but my experiences did not quite coincide with the opinions of those who had written on the disorder, and this experience had, unfortunately, compelled me to come to the conclusion that until something more was known than I had learned from the writings of others, or from my own previous observations, there was no chance of escape from the annual torment. I had thus a personal interest in getting a more thorough knowledge than I then possessed of all the phenomena of hay-fever; and whilst I was in this way furnished with a good and sufficient reason for commencing the investigations, the annoyance caused by the annual attacks acted as a powerful stimulus to exertion in making these as complete as my somewhat limited time and opportunities would permit." (2, page 8-9)

It was this frustration that inspired him, in 1859, to begin a series of experiments to learn the true nature and cause of hay fever, of which he referred to as cararrhus aestivus. (2 page 7)

He initially wanted to perform these experiments on others, although he had only a few volunteers.  So he ultimately decided to perform these them on himself.  This decision was initially criticized by his peers, although they quickly rescinded their criticism as soon as they learned how well his experiments were formulated.

While he initially suspected the experiments would be done quickly, he said that circumstances beyond his control forced them to be done slowly over the course of many years.  He had to test pollen under various situations, and in various seasons.

Likewise, while many of the substances did not cause hay fever symptoms, some of them did cause symptoms that were quite unpleasant.  For instance, when he and his friends were sitting in a room inhaling the odors of Chamomilla metricaria, he started to feel...

...severe aching pain across the forehead, with nausea, dizziness, and pain at the epigastrium... and these became so unpleasant on the second day after the plant had been placed in the room that I was glad to have it removed.  (1, page 57)

Occasional set backs like this would delay further experimentation until he was feeling better. All in all, it took fourteen years for him to conclude his experiments and finish writing his book. (2, page 9)

Blackley was initially criticized for his work.  However, his book was so well written, and his experiments so well performed, that the criticism was not long lasting.

References:

1. "Charles Harrison Blackley, 1820-1900," The University of Manchester: The John Ryland University Library: Manchester Medical Collection, http://archives.li.man.ac.uk/ead/search?operation=full&rsid=dc.title%20any%2Frelevant%2Fproxinfo%20%22William%20Charles%20Henry%22&firstrec=1621&numreq=20&highlight=1&hitposition=1638, accessed 9/13/14
2. Blackley, Charles Harrison, "Experimental Researches on the Causes and Nature," 1873, London, Bailliere, Tindall, and Cox
3. Waite, K.J., "Blackley and the development of hay fever as a disease of civilization in the nineteenth century," Medical History, April, 1995, 39 (2), pages 186-196, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1036974/?page=5, accessed 9/14/14
4. Smith, William Abbotts, "On Hay-Fever, Hay-Asthma, or Summer Catarrh," 1867, London, Henry Renshaw, pages 17-24.
5. Blackley, Charles Harrison, "Hay Fever: It's causes, treatment and effective prevention," 2nd edition, 1880, London, Bailliere, Tindall, & Cox

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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

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